cir annual report 2014

CIRANNUALREPORT

2014RESEARCH GROUPS

PUBLICATIONSDISSEMINATION

ACTIVITIESABOUT

Centre for Im

mune R

egulation (CIR

) | Annual report 2014

Centre for Immune Regulation

VISION STATEMENT

This centre identifies and investigates novel mechanisms of immune dysregulation to advance the development of therapeutics.

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| ANNUAL REPORT 2014 | CENTRE FOR IMMUNE REGULATION (CIR)

n We described and characterized Id-driven T B collaboration as a drive for anti-dsDNA B cells in the systemic autoimmune disease Lupus, demonstrating clonal expansion in lupus-prone mice – both in terms of BCR sequences and by demonstrating anti-dsDNA B cells in functional assays and flow cytometry.

n Published an Ig double knock-in mouse with an anti-Id BCR. Used this mouse to show that Id-specific T and B cells can recognize Id+Ig via conventional mechanisms for

T-B collaboration. Importantly, dendritic cells are not needed for such collaboration.

n Monoclonal antibodies were cloned from single gluten-specific plasma cells isolated from coeliac lesions (Nat Comm 2014). Gluten-specific IgA were found to have restricted VH/VL usage and limited numbers of mutations.

n Increased our understanding of the interaction between the serum half-life regulating receptor, FcRn, and albumin. Designed

and characterized novel albumin variants with increased binding to FcRn that will be used as carriers of biopharmaceuticals to increase their serum half-life.

n Defined a role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa.

n Showed that a specific Rab, important in dendritic cells, interacts with the cytoskeleton and regulates both actin organization and cellular migration.

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2014


2014 has been an active year for CIR. Perhaps the most memorable event was when its members gathered at the end of August for a retreat at Soria Moria. The three Scientific Advisory Board members Sirpa Jalkanen, Søren Buus and Rikard Holmdahl took part in the meeting. They discussed science with CIR scientists and they met with group leaders to advice on scientific matters and priorities to be made within the Centre. Rudolf Valenta from Austria gave a keynote lecture, as did Rikard Holmdahl. The retreat was organised by an organising committee together with Anders Sandvik. They did an excellent job and I thank them for their effort.

There have been a number of scientists who have visited CIR during the year to give guest lectures. These include Jacques Neefjes, Kunchithapadam Swaminathan, Matthew Collin, Patrick Holt, Ralf Küppers, Yueh-Hsieu Chien, Ana-Maria Lennon-Dumenil, Gur Yaari and Gabriel Victora. Most of the speakers were invited to take part in a seminar series organised by a postdoctoral committee. I take the opportunity to thank this committee for conducting this task which is of immense importance to CIR.

In my comments from last year I described the effort we have made to recruit new faculty to CIR. Due to space constraints at the premises of CIR, the Board of CIR decided that rather than advertising a full professorship position, an associate professorship for a junior faculty member should be advertised.

This was done in the autumn of 2014, and 10 applicants had submitted their application by the deadline. On writing these comments, I have just learned that the selection board has submitted their recommendation for the rank order of the best-qualified applicants. Interviews will be made shortly and a candidate will be offered the position before the summer. This person then will have the opportunity to work two and half year at CIR before our Centre is history.

In 2014, CIR scientist authored or co-authored 47 papers in international peer reviewed jour-nals. Two PhD students defended their thesis in 2014; Synne Jenum and Astrid Tutturen. I congratulate the candidates and their super-visors. I also thank the opponents for their effort in evaluating the work of our candidates.

Our Visiting Professor programme had visits from Mark Davis (Stanford) and Susan K. Pierce (NIAID, NIH) in 2014. In 2015 we expect revisits from Mark Davis (Stanford) and Bana Jabri (University of Chicago) as well as a visit by Bernhard Malissen (Centre d'Immunologie de Marseille-Luminy, France) who will be a new Visiting Professor at CIR.Anders Sandvik left his position as adminis-trative coordinator of CIR. He got an exciting job offer from industry. I wish Anders the best of luck in his new job, and thank him wholeheartedly for the excellent job he did for us. We have been very fortunate what regards Anders’ successor – Lise Kveberg. Lise was working as an experienced postdoc in a neighbouring group at the Department of Immunology. Knowing her qualifications we successfully managed to convince her that the position as administrative coordinator of CIR would be a perfect next job station. The transition has been seamless.

Ludvig M. Sollid Centre Director

DIRECTOR’S COMMENTS

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The Research Council of Norway has announced that the forth call in the Centre of Excellence (SFF-IV) scheme. Applicants will qualify in a two step application procedure. The deadline for the first step application will be in November 2015. My hope is that the members of CIR will not be too distracted by this fact and that the inner life of CIR can continue undisturbed. I know there are many interesting project running that deserve to receive our full attention. I hope 2015 will be an interesting and rewarding year for all the scientists at CIR.

Vision statement 3Key accomplishments 2014 3Director’s comments 4Scientific currency 6Innovation and industrialisation 8Core competency 12

RESEARCH GROUPS Bakke group 16Bogen group 18Jahnsen group 20Munthe group 22Sandlie group 24Sollid group 26

ABOUT CIR Facts and figures 30Funding and expenditures 31Staff and students 32Collaboration 34Education and career development 36

ACTIVITIES Visiting Professor program 40Minisymposium 40Work package (WP) symposia 41Guest lectures 42Internal activities 43

PUBLICATIONS Papers in scientific journals 46Other papers 48Books and book chapters 48Patents 49

DISSEMINATIONInvited lectures 52Oral presentations 53Poster presentations 54Other presentations 55Presentations to a targeted audience and the public 55Media coverage 56

CONTENTS


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PAPERSCIR scientist authored or co-authored 47 papers in international peer-reviewed journals in 2014. The total number of publications per year remains stable. Of the papers published in 2014, four publications reached journals with an impact factor above 10.0 and more than one third of the publications reached journals with an impact factor above 5.0. In general the quality and visibility of publications from the centre is high. CIR scientists have exten-sive collaborations with national and inter-national research groups. Close to 6 of 10 papers published in 2014 with one or more CIR authors are the result of collaborations with international institutions.

Impact factor distribution and publications based on collaborations is illustrated in the figures below. CIR publications in 2014 are presented on page 4 of this report. National and international collaborators are listed on page 4.

PATENTSResearchers at CIR have a strong interest in, and record of, innovation and securing of intellectual property rights from research. The accumulated number of patents granted or patent applications filed by CIR scientists since CIR commenced operations is 28. Read more in the innovation and industrialisation section on page 4.

DISSEMINATION OF RESEARCH RESULTSCIR members gave 32 talks as invited speak-ers at international scientific meetings in 2014. In addition 12 oral presentations and 20 posters were presented by CIR scientists at international conferences. Furthermore, CIR staff gave 25 lectures and articles aimed at a targeted audience and the general public. These include postgraduate lectures, re-search seminars, training courses at univer-sities and hospitals, as well as presentations to patient organisations and professional organisations. Talks, posters and dissemina-tion activities aimed at a targeted audience and the public, as well as media coverage, are listed in the back of this report.

PRIZES AND AWARDSCIR scientist Inger Sandlie received the Inven2 honorary award. In 2011, Inger Sandlie was the first to receive UiOs inno-vation prize, and now she received an honorary award for the registration of a total of 100 innovational ideas to Inven2. The prize was presented at the Cutting Edge/Oslo Innovation Week at Forskning-parken in October.

The Oslo University Hospital’s Excellent Researcher Award 2014 was awarded to CIR Director Ludvig M. Sollid for his outstanding research on the pathogenesis of celiac disease. The prize was presented at a staff meeting in August at Oslo University Hospital, Rikshospitalet.

Professor emeritus Per Brandtzæg was awarded the Nordic Fernström prize 2014 for his major contribution throughout his career to the understanding of the role and function of the immune system in the intestinal mucosa.

SCIENTIFIC CURRENCY

Impact factor distribution – CIR publications 2014

No IF available

5–10

<5

>10

57%28%

9%6%

CIR publications with collaborating institutions 2014

International

International and national

National

CIR-only

19%

19%

9%

53%

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Cinzia Progida was awarded the Research prize from Lab Norge 2014 for her work on molecular mechanisms for intracellular transport. This prize is given to stimulate young scientists below 35 years.

CONTRIBUTION TO LOCAL RESEARCH ENVIRONMENTCIR supports the Norwegian Society for Immunology (NSI) and has the ambition to contribute to the whole immunological research environment in Oslo. CIR members are collectively members of the NSI and the centre co-host lectures with the society. Importantly, guest lectures and mini sym-posia hosted by CIR are open to anyone interested and we actively invite the broader immunology community to attend these events. Furthermore, we also invite researchers from outside the centre as speakers at these open events.

Centre staff is involved in the education and supervision of basic scientists and clinicians at all levels. CIR scientists have organised or lectured at graduate courses in molecular cell biology and immunology including Basic immunology and immunological techniques and Advanced immunology offered by the University of Oslo.

CIR staff manages and operates advanced technology and share their technical expertise with the surrounding research environment. CIR group leader Oddmund Bakke heads an advanced imaging platform specialising in subcellular studies of live and fixed cells. In 2013, the NorMIC-UiO imaging platform opened as a national facility. CIR group leader Frode Jahnsen is head of the Confocal microscopy Core facility at the Department of Pathology, offering services within confocal laser scanning microscopy. CIR scientist Gustavo De Souza heads the Proteomics Core facility at Department of Immunology. The facility offers advanced analysis of proteins and peptides by mass spectrometry.

FOCIS-COECIR is a Federation of Clinical Immunology Societies (FOCIS) Centre of Excellence (FCE) (www.focisnet.org). The FCEs represents an exclusive community of institutions of outstanding clinical and scientific quality. There are 70 FCE’s worldwide, with approx-imately 45 centres in North-America and 20 in Europe. The FCE status represents an international recognition of the quality and impact of CIR and provides an opportunity for CIR to strengthen our translational immunology activities.

Annual Report

IRCentre for Immune Regulation

2010

Centre for Immune Regulation (CIR)

Above: Oslo 14.10.2014, Oslo Innovation Week. Cutting Edge: Inger Sandlie, winner of Inven2 Ærespris 2014. Photo: Gorm K. Gaare.

Top: Edward Leithe, Institutt for kreftforskning (Early Career Award 2014)Ludvig M. Sollid, Avdeling for immunologi og transfusjons-medisin (Excellent Research-er Award 2014)Kyrre Eeg Emblem, Inter-vensjonssenteret (Early Career Award 2014)Photo: Ram Gupta/OUS

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NEXTERA ASPhage display is the dominating technology for discovery and refinement of novel protein-based diagnostics and therapeutics. A significantly improved version termed SSIp display has been developed by the Sandlie group at CIR, and commercialized by a spin-out company, Nextera AS. Nextera was estab-lished by key inventor CIR scientist Geir Åge Løset and Biomedical Innovation AS, and Geir Åge Løset has been the Chief Scientific Officer since the company was established in 2009. Additional jointly developed IPR was aquired from Affitech AS in 2012 and Nextera has furthermore inlicensed innovations related to MHC class II through Inven2. These were jointly developed by the Sandlie and Bogen groups at CIR. Through 2013, Nextera were granted patent rights to W02009/024591, WO2010/097411, WO2010/097589, WO2011/036555 and WO2011/101681. The technology platform is continually strength-ened and national IPR was granted in several major countries in 2014.

The core activity of the company is presently focused on phage display of T cell receptors and MHC class II molecules, socalled Phagemers.

Nextera AS is performing joint research with the Sollid and Sandlie groups at CIR partially funded by a major NRC BIA grant using Phagemers with the aim of developing novel therapeutics for Crohns disease. In 2013 Nextera raised 550 000€ in private equity which secures continuous funding of research activities, as well as strengthening the Board of Directors, management and R&D team.

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INNOVATION ANDINDUSTRIALISATION

VACCIBODY ASTwo of the CIR groups (Bogen and Sandlie) have developed novel vaccine molecules, known as Vaccibodies, which induce superior immune responses in a variety of animals. A spin-out company, Vaccibody AS, was founded in 2007 based on the patented technology. Vaccibodies target antigen pre-senting cells for efficient delivery of antigen and induction of immune responses. The vaccines are delivered as DNA plasmids administered intramuscularly or intra-dermally. The muscle or skin cells produce and secrete Vaccibody proteins that target antigen presenting cells and load them with antigen for presentation to lymphocytes.

The patent portfolio is continuously strengthened with clinical use and novel targeting units for a variety of applications. In 2014 the European Patent Office granted European patent No. 1599504 and the U.S. Patent Office issued patent No. US 8,932,603 B2, covering the Vaccibody format. The patent protects Vaccibody’s platform tech-nology on which the company has based its lead human drug candidate VBV1016, as well as a license agreement with the Phibro Animal Health Corporation, covering vaccines for poultry. The company has made significant progress with VBV1016, a therapeutic vaccine against cervical pre-cancerous lesions, and plans to initiate its first clinical trial in 2015. Vaccines for other indications within cancer and infec-tious diseases for human and veterinary use are also developed with academic and industrial partners. In July 2014, Vaccibody issued new shares for 35 million NOK. An investment by the Norwegian Cancer Society was instrumental in the process.


EXTENDING IN VIVO HALF-LIFE OF SMALL DRUGSThe efficacy of chemical drugs, peptides, small proteins and engineered antibody fragments are hampered by short serum half-life, ranging from minutes to a few hours. Therefore, strategies to tailor their serum persistence and biodistribution are needed. Inger Sandlie and Jan Terje

Andersen have developed a unique technology that may extend the in vivo half-life of po-tentially all chemical and protein drugs. This will ultimately result in drugs with stabilized serum levels, which means less side effects and less frequent dosing. Together with Inven2, they have signed agreements with Novozymes Biopharma, and together with Novozymes, established a very success ful

INNOVATION ANDINDUSTRIALISATION

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research program. So far, six patent families have been filed by Novo zymes based on the results of the collaborative research.

As a result of this collaboration, Novozymes has launched new products initially named Albufuse Flex and Recombumin Flex, and recently the Veltis® technology. In short, the new products are based on a list of new albumin variants. All have one or more amino acids that differ from normal albu-min. They bind the neonatal Fc receptor with a range of different affinities, and when tested in rats and rhesus monkeys show greatly altered half-life. The best bind-ers have increased and the poorest binder decreased half-life. Now, either genetic fusion (peptide or protein) or chemical conjugation of small drugs to either of these albumin variants will greatly alter the serum half-life of the drug. In 2013 and 2014, new albumin variants have been designed with increased half-life beyond that of earlier versions.

Novozymes presents the technolgy as follows: • Veltis® – engineered albumins for

optimized drug dosing • Veltis® enables you to control dose

frequency, drug tolerability and dose quantity. So, now you can optimize your therapeutic window easily, and naturally.

Novozymes Veltis® is a half-life extension platform based on engineered albumins designed to provide once-weekly, once two-weekly or once-monthly peptide or protein dosing and stricter patient adherence (com-pliance) for improved therapeutic impact. In addition to being developed by world- leading science the technology is also

backed up by the deep technical and regu-latory support available from Novozymes. Furthermore, based on Novozymes' decades-long experience of recombinant albumin GMP manufacturing, the access to large-scale yeast expression and protein production ensures a secure route to commercial exploitation of the system.

The unique advantages provided by Veltis® include:• proven clinical performance with signifi-

cant half-life extension improvement over native albumin and other technologies

• flexible and scalable manufacturing by fusion or conjugation for commercial supply

• long life IPRs• patient-friendly dosing and low risk of

adverse effects• provided by a technology developer with

a strong heritage and track record in commercial albumin supply

Copenhagen, Denmark – 13 March 2014 – Novozymes Biopharma, part of Novozymes A/S, a world leader in bioinnovation, has today announced a collaboration with Jans-sen Research & Development, LLC (Janssen). The agreement will enable Janssen to evalu-ate Novozymes Biopharma’s engineered albumin-based VELTIS™ technology for potential drug candidates.

Novozymes Biopharma has entered a new collaborative research agreement with one of the world’s top vaccine companies. The partnership will enable the company to evaluate Novozymes Biopharma's modi-fied recombinant human albumin VELTIS technology to assess the dosing and perfor-mance of a novel subunit antigen vaccine candidate.

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Trp 59

Trp 61

Trp 61

Trp 51

Trp 51

Trp 53

Val 52

Trp 53Ile 52

His 161

His 166

Glu 163

Trp 59

His 168

Copenhagen, Denmark – 31 March 2014 – Novozymes Biopharma DK A/S, a sub-sidiary of Novozymes A/S, a world leader in bioinnovation, has announced that its albumin-based VELTIS half-life extension technology is being used by GlaxoSmith-Kline in the recently authorized Eperzan® (albiglutide) for the treatment of type 2 diabetes in Europe.

The US Food and Drug Administration (FDA) has granted marketing approval to GlaxoSmithKline's new type 2 diabetes drug, branded Tanzeum in the US and Eperzan in Europe, which uses Novozymes' Veltis technology to achieve an extended half-life that means patients are only required to inject their medication once a week. The FDA approval follows GlaxoSmithKline's announcement in March that albiglutide received marketing authorization in Europe.

PATENTSPatents and filed patent applications by CIR scientists are listed on page 6.

FcRn regulates serum half-life of albumin and IgG. Comparison of human and rat FcRn crystal structures.

The residues shown are involved in albumin binding. The tryptophan residues shown in red make hydrophobic

contacts with albumin. Histidine 166 in human and histidine 168 in rat FcRn regulate the pH dependence of the

inter action. Illustration: Kine M.K. Sand. Modified by Millimeterpress with permission.

Human FcRn

Rat FcRn

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CORE COMPETENCY AT CIR• A wide variety of cellular and humoral

immune assays.• Advanced methods in molecular biology,

proteomics and cellular imaging.• Disease models in humans and animals.

The models are used to understand the molecular mechanisms of immune regulation and autoimmunity.

• Transgenic mouse models.• Functional characterisation of immune

cells in human tissue.• Study of immune molecules and their

intracellular functions in antigen presenting cells.

• Molecular engineering for the develop-ment of new therapeutic agents and research reagents.

JAHNSEN GROUP• Human model of

airway allergy in vitro and in vivo

• Mucosal antibody system• Dendritic cells

• Immunohistochemistry• Flow cytometry

SOLLID GROUP• Human cellular

immunology• In vitro study of CD4+ T cells

• Recombinant soluble HLA molecules

• Mass spectrometry and proteomics

• Characterisation of lymphocyte antigen

receptors

MUNTHE GROUP• Cellular assays

• Mouse experiments including xenograft

• Cell culture, functional biology• Flow cytometry

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CIR

The centre consists of research groups with complementary scientific expertise. Two groups, headed by Inger Sandlie and Oddmund Bakke, are affiliated with the Department of Biosciences at the Faculty of Mathematics and Natural Sciences. Three research groups, headed by Bjarne Bogen, Ludvig A. Munthe and Ludvig

Sollid are affiliated with the Department of Immunology at the Faculty of Medicine. One group, headed by Frode L. Jahnsen, is a member of the Laboratory for Immunohistochemistry and Immunopathology, Department of Pathology, at the Faculty of Medicine.

BAKKE GROUP• Live cell Imaging

• Confocal microscopy• Characterisation of intracellular

trafficking pathways• Transfection of cells and

the study of binding kinetics of cytosolic molecules

SANDLIE GROUP• Structure and ligand binding properties of

antibodies and T-cell receptors• Phage display

• Recombinant molecule expression and purification

• Interaction studies

BOGEN GROUP• Cellular immunology• Experimental studies

in mice• Transgenic mice

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RESEARCHGROUPS

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RESEARCHGROUPS

BAKKEGROUP

Our group has since the early nineties aimed to understand the endocytic pathway and how peptide loading of the MHC class II complexes (MHC II) is regulated. A special focus for the group is to elucidate the contribution of the invariant chain (Ii) to the biogenesis of an antigen presenting cell (APC) specific endocytic pathway (Landsverk et al., 2009, 2011, 2012).

OVERVIEW OF RESEARCH IN THE GROUP Invariant chain (Ii) plays a vital role in MHC II assembly and intracellular transport, but has been attributed an increasing number of additional functions in both antigen pres-entation, cell signalling and as a vehicle for loading antigens in immunisation protocols. An evolutionary conserved property of Ii is to induce the convergence, or fusion of early endocytic vesicles, and this property may serve vital functions in antigen presentation, cell signalling and beyond. Further more we study the influence of other regulatory molecules essential for the antigen loading compartment such as the small GTP-ases (Berg-Larsen et al., 2013, Borg et al., 2014). The group consist of 2 researchers, 2 post-docs, 2 PhD students, 4 master students and 2 technicians. The Bakke group also runs the NFR- INFRASTUCTURE supported Norwegian Molecular Imaging Consortium, NorMIC-Oslo. NorMIC-Oslo opened as a national imaging facility in 2013 and was in 2014 recommended to become an Eurobio-imaging node in a pan European network of imaging nodes.

KEY PROJECT SUMMARIES• The group is focusing on the properties of

the endosomal pathway in cells in general and the adaptations to this pathway in immune cells. The projects can be divided into five sub themes:

• Sorting and trafficking of immune mole-cules in model cell lines and in dendritic cells.

• Regulation of vesicular transport between the Golgi network and the endosomal and auophagosomal pathway searching for new players.

• Study of endosomal maturation and how the antigen loading compartment, the immunoendosome, is formed.

• Regulation of receptor signalling by endocytic sorting and endosomal effector kinetics in the endosomal pathway.

• Investigation of the mechanisms by which activated macrophages kill cancer cells in mice and humans.

Our work is primarily focused on under-standing the process of antigen uptake, processing and presentation. These events are instrumental to the initiation and prop-agation of adaptive immune responses. The endocytic pathway common to all cells is uniquely adapted by specific immune cells to achieve this purpose. In order to achieve our ultimate goals with regard to discover-ing the specifics of immune cell functions, we have invested a large body of research on how the endocytic pathway functions in general in model cell systems. We have contributed to the current understanding of cell biological processes in the endo-cytic pathway in general and our current goal is to use this foundation to elucidate the unique adaptations to this system in antigen-presenting cells. This will provide the basis to better understand vaccination regimes and protocols for immune therapy of cancers, autoimmune-, and infectious diseases.

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Oddmund Bakke

Our main strategy employs a wide array of advanced live cell imaging technologies, supplemented by biochemistry, immuno-logical assays and DNA/RNA techniques. The group collaborates in studies within CIR, where we provide the cell biological outlook and essential microscopy expertise. These include:• Uptake and sorting of targeted antigen

(Bogen).• B lymphoma cells with complementary

BCRs delete each other in vitro (Jacobsen/ Bogen)

• Intracellular trafficking of the FcRn receptor (Andersen/ Sandlie)

CENTRAL PUBLICATIONS IN 2014 Borg M, Bakke O, Progida C (2014) A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration. J Cell Sci.;127:4927-39

Knudsen Sand KM, Landsverk OJ, Berg-Larsen A, Bakke O, Gregers TF. (2014) The human-specific invariant chain isoform Iip35 modulates Iip33 trafficking and func-tion. Immunol Cell Biol. 2014 92:791-798.

Wälchli S, Kumari S, Fallang LE, Sand KM, Yang W, Landsverk OJ, Bakke O, Olweus J, Gregers TF (2014) Invariant chain as a vehicle to load antigenic peptides on human MHC class I for cytotoxic T-cell activation. Eur J Immunol. 44, 774-84.

ACHIEVEMENTS IN 2014• Showed that a specific Rab, important

in dendritic cells, interacts with the cytoskeleton and regulates both actin organization and cellular migration (J Cell Science, 2014).

• Described how the human specific form of invariant chain may influence the trafficking of other forms of the molecule and thereby trafficking of MHC II (Immunol and Cell Biol, 2014).

• Developed a patented and invariant chain based vector for immune therapy against cancer (Patent submitted).

AMBITIONS FOR 2015• Dissect elements of the molecular

mechanisms for sorting to the intracellular antigen loading compartment based on high throughput antigen loading screens.

• Using an autophagosomal interaction partner of Rab7B we will elucidate how autophagy is connected to transport from the trans Golgi network.

• Characterise endosomal maturation in dendritic cells and the Meljuso model antigen presenting cells. Define a pathway to the MHC II antigen loading compart-ment.

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BOGENGROUP

INTROImmunoglobins (Ig, antibodies) are extremely diverse, the heterogeneity being localized to their variable (V) regions. Bogen and co-workers showed more than 25 years ago that Ig is partially broken down inside cells and that proteolytic fragments of the V-regions [Idiotypic (Id)-fragments] are pre-sented on Major Histocompatibility Complex (MHC) class II molecules to Id-specific CD4+ T cells. This phenomenon forms the foun-dation for the CIR-related projects of the research group, outlined below.

KEY PROJECT SUMMARIESThe basis for Id-driven T-B collaboration is that B cells spontaneously degrade their Ig-receptor for antigen (BCR), and display Id-peptides bound to MHC class II molecules on their cell surface. Such Id/MHCII com-plexes can be recognized by Id-specific CD4+ T cells. Now, if a B cell happens to recognize a self-antigen with its BCR, and at the same time receives help from an Id-specific CD4+ T cell, the B cell receiving these two distinct signals will be activated, proliferate and differentiate. This may result in immune dysregulation, autoimmunity and B lym-phoma development. To study Id-driven T-B collaboration in even more detail, we have generated novel BCR knock-in mice. In one of these strains, a mutated Id-sequence (3 amino acids) have been successfully inserted in a germ-line V gene segment. The latter mouse should represent a close to physi-ological model for Id-driven T-B collabora-tion. A project on elucidation of the ternary Id-specific TCR/Id-peptide/MHC class II (I-Ed) molecule is in progress (with Inger Sandlie). Id-driven T-B collaboration is now being

extended to human autoimmune disease and lymphoma development in collaboration with Ludvig Munthe (see his report)

The basis for the tumor immunological experiments of the group is that Ig secreted by multiple myeloma cells (malignant plasma cells) is processed and presented on MHC class II molecules of tumor-infiltrating macrophages. An interplay between Id-spe-cific CD4+ T cells and macrophages results in activation of macrophages that in turn kill the tumor cells. In 2014 we have reported that the above described mechanism does not confer bystander killing of antigen- negative tumor cells. Moreover, we have detected a mechanism by which tumor cells can escape killing by CD4+ T cells. Ongoing experiments focus on the molecular mecha-nisms by which activated macrophages kill tumor cells. A bone-marrow model for multiple myeloma (the MOPC315.BM model), published by our group in 2012, has now been distributed to a large number (>20) collaborators world-wide. Our group is doing work in this model, and we have demonstrated that CD4+ T cells can kill tumor cells residing in the bone marrow. Internationally, it is now increasingly recognized that CD4+ T cells play an important role in rejection of tumors, also in humans.

CENTRAL PUBLICATIONS IN 2014Jacobsen J, Haabeth OA, Tveita AA, Schjetne KW, Munthe LA, Bogen B.Naive idiotope- specific B and T cells collaborate efficiently in the absence of dendritic cells. J Immunol. 2014 ,192(9):4174-83. PMID: 24706724

The Bogen group runs projects with three areas, 1) Idiotype-driven T-B collaboration and its role in health and disease, 2) The mechanism by which CD4+ T cells can reject cancer cells, 3) Novel vaccine molecules for cancer and infectious diseases (organized in K.G. Jebsen Centre for Research on Influenza Vaccines).

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Bjarne Bogen

Tveita AT, Schjesvold FM, Sundnes O, Haabeth OAW, Haraldsen G, Bogen B. Indirect CD4+ T cell-mediated elimination of MHC IINEG tumor cells is spatially restricted and fails to prevent escape of antigen- negative cells. Eur. J. Immunol, Sep; 44(9): 2625-37. PMID: 24846412

Ruffini PA, Os A, Dolcetti R, Tjonnfjord GE, Munthe LA, Bogen B. Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice. Journal of Transla-tional Medicine. Jul 25;12:207, 2014, PMID: 25059102

Fossum E, Grødeland G, Terhorst D, Tveita AA, Vikse E, Mjaaland S, Henri S, Malissen B, Bogen B. Vaccine molecules targeting Xcr1 on cross-presenting DCs induce protective CD8+ T-cell responses against influenza virus. Eur J Immunol Nov 20 doi:10.1002/eji.201445080 [Epub ahead of print] PMID: 25410055

ACHIEVEMENTS IN 2014• Published an Ig double knock-in mouse

with an anti-Id BCR. Used this mouse to show that Id-specific T and B cells can recognize Id+Ig via conventional mecha-nisms for T-B collaboration. Importantly, dendritic cells are not needed for such collaboration.

• Established an Ig VH knock-in mouse that, when bred with 2315-transgenic mice, establishes a model for an Id+ BCR.

• Established a knock in mouse where 3 mutated amino acids have replaced 3 germline-encoded residues in a V gene segment. This is the first time such a knock-in has been generated. The mouse should be an important tool for studies on Id-driven T-B collaboration.

• Published that the CD4+ T cell/macrophage mechanism for tumor cell killing does not confer elimination of antigen-negative tumor cells.

• Detected a molecular mechanism by which tumor cells can escape elimination by CD4+ T cells/macrophages.

AMBITIONS FOR 2015• To investigate the importance of BCR-

ligation by self-antigen in Idiotype- driven T-B collaboration, using the new BCR knock-in mice described above.

• To study interaction of B cells with complementary BCRs by use of the knock-in mice generated in 2014.

• To explore the molecular mechanism by which CD4+ T cells reject tumour cells.

• To study CD4+/macrophage-mediated elimination of tumor cells in the bone marrow.

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JAHNSENGROUP

OVERVIEW OF RESEARCH IN THE GROUP The turn-over rate of immune cells in the human body is an important characteristic of their function. However, surprising little is known about the turn-over and long-evity of human immune cells. In collabora-tion with surgeons at the hospital we have established several new methods to study the longevity of immune cells in various human tissues, both during homeostasis and inflammation.

KEY PROJECT SUMMARIESBy isolating cells from surgical specimens (cancer surgery and transplanted patients) we have been able to perform detailed characterization of immune-cell subsets (B cells, macrophages and dendritic cells) in the human small intestine and determined their phenotypic characteristics, their differentiation, longevity and replacement kinetics. Such studies have never before been performed in humans. We show that proinflammatory monocytes are constantly recruited to the intestinal mucosa and that they over weeks differentiate into anti-inflammatory macrophages. All sub-populations of intestinal dendritic cells are constantly being replaced by their pre-cursors in blood with a very rapid turnover rate. Together, our results demonstrate that mononuclear phagocytes in the human gut consist of many functionally distinct sub-sets. Importantly, we find that plasma cells in the gut are very long-lived (>> 1 year). This finding is surprising and may have im-portant implications for future vaccinations strategies.

Lymphocyte recruitment to peripheral tissues is fundamental for immune surveil-lance and homeostasis, but the chemokines and chemokine receptors responsible for tissue-specific homing of T cells to the upper airway mucosa have not been determined. We found that CCL28 is preferentially expressed on endothelial cells in the mucosa and its receptor CCR3 is expressed on the majority of mucosal T cells. Functional studies indicate that CCL28-CCR3 interactions are involved in the homeostatic trafficking of CD4(+) T cells to the upper airways.

In an experimentally-induced human model for allergic rhinitis we find that CD14+ monocytes are rapidly (within hours) recruited to the nasal mucosa in response to allergen challenge in allergic patients. By transcriptomic profiling we find that mono-nuclear phagocytic cells in the challenged nasal mucosa produce several Th2-associated chemokines during the inflammatory reaction, suggesting that these cells, including monocytes, are central players as proinflammatory cells in upper airway allergy recruiting and activating Th2 cells and eosinophils.

CENTRAL PUBLICATIONS IN 2014Jenum S, Grewal HM, Hokey DA, Kenneth J, Vaz M, Doherty TM, Jahnsen FL, TB Trials Study Group (2014). The frequencies of IF-Nγ+IL2+TNFγ+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® gold in-tube response in a prospective study of healthy indian adoles-cents. PLoS One 9 (7), e101224

We study the mucosal immune system in the human gut and airways both under homeostatic conditions and during inflammation.

22


Frode Jahnsen

Melum GR, Farkas L, Scheel C, Van Dieren B, Gran E, Liu YJ, Johansen FE, Jahnsen FL, Baekkevold ES (2014). A thymic stromal lymphopoietin-responsive dendritic cell subset mediates allergic responses in the upper airway mucosa. J Allergy Clin Immunol 134 (3), 613-621.e7

A role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa. Danilova E, Skrindo I, Gran E, Hales BJ, Smith WA, Jahnsen J, Johansen FE, Jahnsen FL, Baekkevold ES. Mucosal Immunol. 2015 Jan;8(1):107-14. doi: 10.1038/mi.2014.46. Epub 2014 Jun 11.

ACHIEVEMENTS IN 2014• Identified monocytes as a central

component of the inflammatory process in allergic rhinitis

• Determined plasma-cell subsets and their longevity in the human small intestine.

• Determined the half-life of monocytes, macrophages and dendritic cells in the human small intestine

• Defined a role for CCL28-CCR3 in T-cell homing to the human upper airway mucosa.

AMBITIONS FOR 2015• Study the blood monocyte compartment

in experimentally-induced celiac disease.• Functional characterization of monocytes,

macrophages and dendritic cells in the human small intestine.

• Explore the relationship of immune cells and stromal cells in experimentally- induced allergic rhinitis.

• Explore the relationship of immune cells and stromal cells in active celiac disease.

• Determine the longevity of resident memory T cells in the human small intestine.

Frode Jahnsen

23


OVERVIEW OF RESEARCH IN THE GROUPWe are interested in how Th cells can regulate B cell responses, both in health, in autoimmunity and after malignant transfor-mation. Our goal is to define the specificity of Th cells, the mechanisms of collaboration, to pinpoint targets for pharmacological interventions and to study heterogeneity between patients. We have made important contributions to explain the pathogenesis of CLL and would very much like to extend these results to Multiple Myeloma.

KEY PROJECT SUMMARIES We have the following research questions:• How can Idiotype-specific Th cells drive

autoimmune B cell responses?• How can Th cells drive the proliferation

of human lymphoma?• What is wrong with BCR signalling in

CLL?• What is the drive for myeloma prolifera-

tion in human patients?• How can we identify which drugs can

abrogate lymphoma and myeloma proliferation?

• What allows reversal of B cell anergy in CLL and reversal of anergy in anergic B cell subsets in normals?

CENTRAL PUBLICATIONS IN 2014Aas-Hanssen, K., A. Funderud, K.M. Thompson, B. Bogen, and L.A. Munthe. 2014. Idiotype-specific Th cells support oligo-clonal expansion of anti-dsDNA B cells in mice with lupus. Journal of immunology 193:2691-2698.

Jacobsen, J., O.A. Haabeth, A.A. Tveita, K.W. Schjetne, L.A. Munthe, and B. Bogen. 2014. Naive idiotope-specific B and T cells collabo-rate efficiently in the absence of dendritic cells. Journal of immunology 192:4174-4183.

ACHIEVEMENTS IN 2014• We described and characterized Id-driven

T B collaboration as a drive for anti-dsD-NA B cells in the systemic autoimmune disease Lupus, demonstrating clonal expansion in lupus-prone mice – both in terms of BCR sequences and by demon-strating anti-dsDNA B cells in functional assays and flow cytometry. Aas-Hanssen et al, The Journal of Immunology 2014.

• We demonstrated a novel pathway for ex-pansion and support of chronic lympho-cytic leukemia (CLL) cells from patients, Bürgler et al, The Journal of Immunology 2014. CLL patients have T helper (Th) cells of the Th1, IFN-g secreting type that are specific for CLL cell antigen. When mixed, we show that Th1 cells activate CLL cells in an IFN-g dependent manner and that IFNg activates the T-Bet transcription factor in CLL cells. With ChIP-analysis and qPCR we identify T-Bet consensus sites in intron I of the CD38 gene, demonstrating a IFNG-JAK- T-bet -CD38 axis. Blocking IFNG-g in xenograft experiments abrogated proliferation of cancer cells. We thereby link Th cell activation, cytokine profile and CLL cell response to the CD38 marker that is important for prognosis in the patient group. We also demonstrated that Th cells activate CLL cells to secrete pro-inflammatory chemokines, further attracting CLL cells.

MUNTHEGROUPWe study B cell biology in health, autoimmunity and cancer. As most B cell cancers have autoreactive specificities, the autoimmunity and cancer studies are closely linked. We have progressed to study how Th cells in patients can maintain autoimmune B cells as well as lymphoma cells.

24


• We extended the network of sample collection to South Eastern Norway, adding to our biobank collection.

• We published with the Bogen group on the utility of Vaccibodies in CLL (Ruffini et al, J Transl Med, 2014), on Id-dependent Th B cell collaboration (Jacobsen et al, The Journal of Immunology 2014) and on FAM46 gene variants predisposing to M tuberculosis (Etokebe et al, PlosOne 2014). We contributed to papers to be published in early 2015.

• We published 8 clinical immunology papers (Bazso et al., 2014; Bodolay et al., 2014; Laczik et al., 2014; Nakken et al., 2014; Senolt et al., 2014; Szodoray et al., 2014; Vincze et al., 2014; Zold et al., 2014)

• We obtained funding from the Health Region South East to initiate a Personal-ized Medicine initiative for CLL and myeloma in 2015 (Kjetil Tasken, Geir Tjønnfjord; Miljøstøtte, 9 million NOK).

• We achieved long term culture of CLL cells ex vivo from patients, implemented multiplexed phosphoflow in our analyses

• We initiated collaborations with two biotech companies.

AMBITIONS FOR 2015• We will characterize allelic inclusion,

exclusion and exchange of VL and VH of anti-dsDNA B cells in Lupus mice.

• We will present bioinformatics analyses of Th cell antigens in murine Lupus.

• We will define the mechanism for how B cell anergy is reversed in human anergic B cells, suggest novel druggable targets.

• We will define how a small molecular pathway inhibitor can have effect on CLL cells and not normal B cells, pinpointing a treatment strategy in this disease.

• We will demonstrate how primary mye-loma cells from patients can be stimulated to proliferate in vitro and in vivo.

• We will succeed in establishing ex vivo culture of human primary myeloma cells.

• We will define how EBV infection may play a part in disease progression in CLL.

• We will initiate a high throughput drug screen for CLL (ex vivo culture).

Ludvig A. Munthe

25


SANDLIEGROUP

The Sandlie group studies the structure and function of antibodies and T-cell receptors, the specific detecting molecules of the adaptive immune system. The purpose of the work is to engineer antibodies and antibody derived molecules to be used in therapy and as research reagents.

OVERVIEW OF RESEARCH IN THE GROUPFurthermore, one antibody receptor, the neonatal Fc receptor (FcRn), also binds albu-min, and we study how FcRn binding regu-lates the serum half life and biodistribution of albumin and molecules bound to albumin.

We focus on two projects: A) Studies of the interaction between Fc receptors, and in particular FcRn, with IgG subclasses and albumin. Key questions are how ligand binding elicits antibody effector functions and regulate biodistribution and serum half-life. B) Selection of antibodies for the detection of complexes between antigenic peptides and HLA molecules, as well as peptide – HLA complexes for detection of specific T-cell receptors. The focus is on engineering to increase stability and affinity for molecules that are characteristic of disease models in groups at CIR.

KEY PROJECT SUMMARIESProteins in blood are short lived and nor-mally degrade within a few hours or days, but the two most abundant proteins, IgG and albumin, are rescued from degradation and have half-lives of three weeks. The rescue mechanism depends on their interaction with the neonatal Fc receptor (FcRn), and it is crucial to understand how FcRn rescues IgG and albumin, and to transfer long half-life to therapeutics, using the same mechanism. We have worked in collabora-tion with Novozymes Ltd, UK, who has filed several patent applications and developed the Veltis® technology, a set of human albumin variants designed by us with greatly increased binding affinity for FcRn. Biopharmaceuticals fused to a new albumin

variant can have half-life of months, which will decrease dose, dozing frequency and toxic side effects. In 2014, we reported on the fine mapping of the albumin FcRn interaction.

To ask questions regarding the nature of the antigen presenting cell, the location and rate of antigen presentation and the interaction with T cells, specific detection molecules are needed. Specific antibodies and soluble T-cell receptors are new tools for such studies in health and disease. We have explored how phage display may be used to improve the affinity of antibodies and the stability and affinity of soluble T-cell receptors and MHC class II molecules. We have displayed not only soluble T cell receptors, but also MHC class II molecules, so-called “Phagemers”, which will be used as diagnostics for coeliac disease. Furthermore, a spin-out company, Nextera AS, commercialises and develops the new phage display- and Phagemer tech-nologies, and utilizes libraries of Phagemers to search for disease causing proteins that drive pathological T cell activation in auto-immune diseases and chronic infections.

CENTRAL PUBLICATIONS IN 2014Hallstensen RF, Bergseth G, Foss S, Jæger S, Gedde-Dahl T, Holt J, Christiansen D, Lau C, Brekke OL, Armstrong E, Stefanovic V, Andersen JT, Sandlie I, Mollnes TE. Eculi-zumab treatment during pregnancy does not affect the complement system activity of the newborn. Immunobiology. 2014 Nov 13. pii: S0171-2985(14)00228-9. doi: 10.1016/j.imbio.2014.11.003.

26


Inger Sandlie

Sand KM, Bern M, Nilsen J, Dalhus B, Gun-narsen KS, Cameron J, Grevys A, Bunting K, Sandlie I, Andersen JT. Interaction with both domain I and III of albumin is required for optimal pH-dependent binding to the neo-natal Fc receptor (FcRn). J Biol Chem. 2014 Dec 12;289(50):34583-94. doi: 10.1074/jbc.M114.587675. Epub 2014 Oct 24.

Sand KM, Dalhus B, Christianson GJ, Bern M, Foss S, Cameron J, Sleep D, Bjørås M, Roope-nian DC, Sandlie I, Andersen JT. Dissection of the neonatal Fc receptor (FcRn)-albumin interface using mutagenesis and anti-FcRn albumin-blocking antibodies. J Biol Chem. 2014 Jun 13;289(24):17228-39. doi: 10.1074/jbc.M113.522565. Epub 2014 Apr 24.

Andersen JT, Dalhus B, Viuff D, Ravn BT, Gunnarsen KS, Plumridge A, Bunting K, Antunes F, Williamson R, Athwal S, Allan E, Evans L, Bjørås M, Kjærulff S, Sleep D, Sandlie I, Cameron J. Extending serum half-life of albumin by engineering neonatal Fc receptor (FcRn) binding. J Biol Chem. 2014 May 9;289(19):13492-502. doi: 10.1074/jbc.M114.549832. Epub 2014 Mar 20.

ACHIEVEMENTS IN 2014• Increased our understanding of the

interaction between the serum half-life regulating receptor, FcRn, and albumin. Designed and characterized novel albumin variants with increased binding to FcRn that will be used as carriers of biopharma-ceuticals to increase their serum half-life.

• Demonstrated that the interaction is hydrophobic, and the binding site for FcRn on albumin overlaps with a high affinity binding site for fatty acids. Thus, ligands bound to albumin may well affect its interaction with FcRn, which is important for transport and deposition of ligands at different body sites.

• Selected antibodies that bind specifically to HLA DQ2.5 in complex with gluten peptide.

AMBITIONS FOR 2015• Design improved molecular trackers for

specific peptide – MHC complexes to be used in studies of antigen presentation.

• Design molecular trackers for specific T-cell receptors characteristic for gluten specific T cells to be used in diagnostic tests.

• Analyse the fine specificity of the T cell response in coeliac disease.

• Understand basic mechanisms that govern transcytosis and recycling of albumin and IgG, and how both processes are altered by ligand binding.

• Describe structural features of the con-stant regions of the human IgG subclasses that are important for their effector func-tions, and characterize how IgG bound to certain pathogens directs them to intra-cellular degradation and initiate signalling that alerts the cell to convert to fighting the infection.

27


SOLLIDGROUP

OVERVIEW OF RESEARCH IN THE GROUPThis disorder, caused by an inappropriate immune response to cereal gluten proteins, is characterised by a strong HLA associa-tion and presence of autoantibodies specific for TG2. We have generated a large panel of CD4+ T-cell lines and clones cultured from intestinal biopsy specimens from coeliac disease patients. Characterisation of how these T cells recognise gluten protein has led to interesting findings such as the importance of protein structure on antigen processing, how enzyme mediated post-translational protein modification increases antigenicity and how HLA binding specificity and peptide-MHC stability influence T-cell priming. This knowledge reveals general principles of immune regulation that are applicable to other autoimmune and chronic inflammatory diseases. Currently we have taken up a strong interest in characterising the autoantibody response of coeliac disease. This is the focus of an ERC Advanced Grant project we undertake.

KEY PROJECT SUMMARIESStructure and function of TG2: We are trying to understand where and how TG2 is active in the intestinal coeliac lesions.

Gluten-reactive T cells: We are studying TCR specificity and function of gluten- reactive T cells. MHC tetramers are key tools in these studies.

B cells and plasma cells: We are studying the specificity of human recombinant anti-bodies cloned from immunoglobulin genes of single TG2-specific or gluten-specific plasma cells isolated from gut biopsies.Characterisation of BCR and TCR of anti-

gen-specific cells: High throughput DNA sequencing is implemented to monitor and follow adaptive immune responses.

CENTRAL PUBLICATIONS IN 2014Qiao SW, Christophersen A, Lundin KE, Sollid LM (2014) Biased usage and preferred pairing of – and -chains of TCRs specific for an immunodominant gluten epitope in coeliac disease. Int. Immunol., 26(1):13-9.

Iversen R, Mysling S, Hnida K, Jørgensen TJ, Sollid LM (2014) Activity-regulating struc-tural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange. Proc. Natl. Acad. Sci. U. S. A., 111(48):17146-51.

Dørum S, Bodd M, Fallang LE, Bergseng E, Christophersen A, Johannesen MK, Qiao SW, Stamnaes J, de Souza GA, Sollid LM (2014) HLA-DQ molecules as affinity matrix for identification of gluten T cell epitopes. J. Immunol., 193(9):4497-506.

Christophersen A, Ráki M, Bergseng E, Lun-din KE, Jahnsen J, Sollid LM, Qiao SW (2014) Tetramer-visualized gluten-specific CD4+ T cells in blood as a potential diagnostic marker for coeliac disease without oral gluten challenge. United. European. Gastroenterol. J., 2(4):268-78.

Steinsbø Ø, Henry Dunand CJ, Huang M, Mesin L, Salgado-Ferrer M, Lundin KE, Jahn-sen J, Wilson PC, Sollid LM (2014) Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells. Nat. Commun., 5:4041.

Our group is trying to dissect the interplay of environmental and genetic factors in chronic autoimmune disorders. We are concentrating on coeliac disease as a model to understand the molecular mechanisms leading to chronic inflammatory disease.

28


Ludvig M. Sollid

Amundsen SS, Viken MK, Sollid LM, Lie BA (2014) Coeliac disease-associated poly morphisms influence thymic gene expression. Genes. Immun., 15(6):355-60.

Sollid LM, Pos W, Wucherpfennig KW (2014) Molecular mechanisms for contribution of MHC molecules to autoimmune diseases. Curr. Opin. Immunol., 31:24-30.

Lundin KE, Sollid LM. Advances in coeliac disease (2014) Curr. Opin. Gastroenterol., 30(2):154-62.

ACHIEVEMENTS IN 2014• Monoclonal antibodies were cloned from

single gluten-specific plasma cells isolated from coeliac lesions (Nat Comm 2014). Gluten-specific IgA were found to have restricted VH/VL usage and limited numbers of mutations.

• Completed studies using hydrogen/ deuterium exchange to assess structural changes induced by Ca2+, GTP, cysteine oxidation and by the binding of trans-glutaminase 2 (TG2) autoantibodies of coeliac disease patients on TG2 (PNAS 2014). Binding of Ca2+ and GTP stabilised distinct regions in the catalytic core and C-terminal domains of TG2 and oxidation prevented the Ca2+-induced changes. Binding of TG2 autoantibodies resulted in pronounced allosteric effects on TG2 structure.

• Used proteomics to characterise the endogenous peptide ligands of HLA-DQ2.5, HLA-DQ2.2 and HLA-DQ7.5 (Immunogenetics 2015) and to identify (novel) gluten T-cell epitopes that selec-tively bind to HLA-DQ2.5 and HLA-DQ2.2 (J Immunol 2014). The binding motifs of

HLA-DQ2.5 and HLA-DQ2.2 were found to be different where position P3 was a major anchor site only in HLA-DQ2.2. This data fit with the finding that the three known HLA-DQ2.2-restricted gluten epitopes all harbour serine at P3.

• Measured frequency of gluten-reactive T cells in blood of coeliac disease patients and healthy controls by HLA tetramer staining (United European Gastroenterol J 2014). Showed proof-of principle that the enumeration of gluten-tetramer binding effector memory T cells in blood may be used in coeliac disease diagnosis.

AMBITIONS FOR 2015• Continue with high throughput sequencing

of B-cell receptors (BCR) and T-cell recep-tors (TCR) as well as undertaking paired BCR VH–VL and TCR Va–Vb sequencing from single cells. Complete the study on paired TCR repertoire analysis of DQ2.5-glia-2 and DQ2.5-glia-2-reactive T cells.

• Complete the structural studies of TG2-specific autoantibodies of coeliac disease, and in complex with TG2.

• Perform blinded study on using tetramer-staining of gluten-reactive T cells in blood as potential diagnostic tool in differentiat-ing coeliac disease patients on gluten-free diet and healthy controls.

• Perform in vitro studies to investigate cooperation between TG2-specific B cells and gluten-reactive T cells.

29


ABOUT30


ABOUT31


FACTS AND FIGURESCentre for Immune Regulation (CIR) was established in December 2007 as a Centre of Excellence appointed by the Research Council of Norway. Following a successful midterm evaluation, CIR will continue to operate as a CoE till the end of 2017. CIR is also a FOCIS (Federation of Clinical Immunology Societies) Center of Excellence.Our host institution is the University of Oslo. Oslo University Hospital is an equal consortium partner. The centre is organised directly under the Faculty of Medicine and the centre Director reports to the Dean. CIR comprises research groups from the Faculty of Mathematics and Natural Sciences, the Faculty of Medicine and from Oslo University Hospital. Centre staff is employed at the Department of Biosciences, the Department of Immunology and the Department of Pathology.

107 persons, producing 60.5 person years, are involved in research at CIR.

CIR actively recruits international talents and currently 20 nationalities are represented at the centre.

The overall gender balance at CIR is 37/63 with an overweight of female members among postdocs, PhD students, master students and technicians.

THE RESEARCH GROUPSCIR consists of six research groups headed by professors, Ludvig M. Sollid, Inger Sandlie, Oddmund Bakke, Bjarne Bogen, Frode L. Jahnsen and Ludvig A. Munthe. Professor Ludvig A. Munthe joined CIR as a new group leader in January, 2014. Sollid’s group in-cludes the group of Gustavo de Souza, head of the proteomics core facility and projects. Bakke’s group includes the group of Alex-andre Corthay and Sandlie’s group includes the group of Jan Terje Andersen.

MANAGEMENTThe centre is headed by Director Ludvig M. Sollid and Deputy Director Inger Sandlie. The centre management is supported by an administrative coordinator, Lise Kveberg. The Director has the daily responsibility for project management, administration and delivery.

THE CIR BOARDThe governing board of CIR has four mem-bers; two from the University of Oslo (UiO) and two from Oslo University Hospital (OUS). The board is appointed by UiO. • Hilde I. Nebb (chair), Dean of Research,

Faculty of Medicine, UiO.• Svein Stølen, Dean of Research, Faculty of

Mathematics and Natural Sciences, UiO.• Erlend B. Smeland, Director of Research,

Innovation and Education, OUS.

FACTSAND FIGURES

32


• John Torgils Vaage, Head of the Depart-ment of Immunology, OUS.

The authority of the board is to ensure that the intentions and terms of contract de-scribed in the Centre of Excellence agree-ment are fulfilled. Furthermore, the board approves the annual budget and ensure that centre activities are completed as outlined in the project description and funding plan, within the adopted time frame.

SCIENTIFIC ADVISORY BOARDCIR has a scientific advisory board (SAB) consisting of European world-class scientists. The SAB’s mandate is to critically evaluate and advice on the centre’s scientific perfor-mance and progress. • Professor Søren Buus, University of

Copenhagen, Denmark.• Professor Rikard Holmdahl, Karolinska

Institutet, Stockholm, Sweden.• Professor Sirpa T. Jalkanen, University

of Turku, Finland.

FOCIS COE CLINICAL ADVISORY BOARD AND LAY ADVISORY BOARDAs a Federation of Clinical Immunology Societies (FOCIS) Centre of Excellence (FCE), CIR has established two advisory boards. The clinical advisory board is responsible for facilitating translational research at CIR.

• Head physician Knut E. Lundin (chair, gastro enterologist, OUS).

• Professor II Geir E. Tjønnfjord (haema-tologist, OUS and UiO).

• Professor Knut Dahl-Jørgensen (paediatri-cian, OUS and UiO).

• The lay advisory board focuses on strate-gic development, fundraising and community outreach.

• The Director of the Norwegian Coeliac Society.

• The Secretary General of the Norwegian Asthma and Allergy Association.

• The Secretary General of the Norwegian Diabetes Association.

FUNDING (1000 NOK) 2014Research Council of Norway (RCN) – CoE 1 11050University of Oslo (UiO) 2 19686Oslo University Hospital (OUS) 3 9086Other funding from RCN 7323South-Eastern Norway Regional Health 12811Private funding 4 2857International funding 5 7749Total funding 70562

1 Centre of Excellence grant.2 Including value of personnel funded by UiO and indirect costs of infrastructure.3 Including value of personnel funded by OUS and indirect costs of infrastructure.4 Including grants from the Norwegian Cancer Society, and others. 5 Including ERC advanced grant, EU grants, and others.Compared to 2013, the total funding is increased in 2014.

33


GROUP LEADERSName Position Funding* Employer*Oddmund Bakke Professor UiO UiOBjarne Bogen Professor UiO/OUS UiO/OUSFrode L. Jahnsen Professor UiO/OUS UiO/OUSInger Sandlie Professor UiO UiOLudvig M. Sollid Professor RCN-CIR/ERC UiOLudvig A. Munthe Professor UiO UiO

RESEARCH SCIENTISTS

Name Position Funding* Employer*Per Brandtzæg Professor emeritus Espen Bækkevold Researcher S-EN RHA OUSAlexandre Corthay Researcher RCN OUSGerbrand Koster Researcher RCN UiOKnut E.A. Lundin Consultant S-EN RHA OUSGeir Åge Løset Researcher RCN UiOIngrid Olsen Researcher RCN UiOShuo-Wang Qiao Researcher UiO UiOGustavo de Souza Researcher UiO UiOKeith Thompson Researcher UiO UiOInger Øynebråten Researcher S-EN RHA OUSJan Terje Andersen Researcher RCN OUS

STAFF AND STUDENTS

CIR STAFF DEVELOPMENT

20142008 2009 2010 2011 2012 2013

140

120

100

80

60

40

20

0

Head count

Man years * Headcount includes unpaid MSc/MD students and staff that left or

joined CIR during 2014.

CENTRE PERSONNEL 2014

Group

lead

ers

Resea

rche

rs

Postd

ocs

PhD st

uden

s

MSc/MD st

uden

ts

Tech

nician

s

Admini

strati

on

35

30

25

20

15

10

5

0

6

13

20

29

18 18

1

34


Peter Szoroday Researcher OUS OUSDong Wang Researcher RCN-CIR UiO

TECHNICIANS Name Position Funding* Employer*Frode M. Skjeldal Senior engineer UiO UiOLinda Haugen Senior engineer UiO UiOKahsai Beraki Senior engineer UiO UiOIngrid Kjos Staff engineer RCN-CIR UiOHilde Omholt Senior engineer NCS OUSMarte Fauskanger Research assistent S-EN RHA OUSAaste Aursjø Senior engineer UiO UiOKathrine Hagelsteen Biomedical Laboratory Scientist UiO UiOLinda I. Solfjell Biomedical Laboratory Scientist OUS OUSKjersti Thorvaldsen Hagen Biomedical Laboratory Scientist S-EN RHA OUSHege Eliassen Senior Executive Officer UiO/OUS UiO/OUSSara Halmøy Bakke Staff engineer UiO UiOSathiyaruby Sivaganesh Staff engineer UiO UiOMarie K Johannesen Senior engineer UiO UiOBjørg Simonsen Staff engineer S-EN RHA OUSMaria Ekman Stensland Staff engineer S-EN RHA UiOMartin McAdam Research Technician RCN OUSStine Rosenqvist Lund Engineer S-EN RHA OUS

ADMINISTRATION

Name Position Funding* Employer*Lise Kveberg Senior advisor RCN-CIR UiO

POSTDOCS

Name Funding* Employer*Cinzia A. M. Progida RCN/CIR/UiO/NCS UiOCathrine Hayward UiO UiOAnders A Tveita NCS OUSJohanne Jacobsen S-EN RHA OUSOle-Audun W. Haabeth S-EN RHA OUSPeter C. Huszthy RCN UiOLisa M. Gruber S-EN RHA OUSOle J.B. Landsverk S-EN RHA OUSKristin Gunnarsen S-EN RHA OUS

GENDER BALANCE STAFF

Group

lead

er

Resea

rche

r

Postd

oc

PhD st

uden

t

Studen

t

Tech

nician

Master

stud

ent

Admini

strati

on

GENDER DISTRIBUTION

Female

Male

20

18

16

14

12

10

8

6

4

2

0

CIR – Centre for Immune RegulationERC – European Research Council, Advanced grantEU – European UnionS-EN RHA – South-Eastern Norway Regional Health AuthorityNCS – Norwegian Cancer SocietyOUS – Oslo University HospitalRCN – Research Council of NorwayImmusanT – Biotechnology company, UKUiO – University of OsloUEG – United European Gastroenterology

The list of CIR staff and students include both mem-bers that left and joined the Centre during 2014. Several CIR members have changed employer, position and fund-ing body during 2014. The listed funding body, position and employer refer to the status per December 2014.

37%

63%

35


COLLABORATIONNATIONALMagnar Bjørås, Dept. of Microbiology, Oslo Univ. Hosp. and Univ. of OsloHeidi Kiil Blomhoff, Institute of Basic Medical Sciences, University of Oslo Rune Blomhoff, Institute of Basic Medical Sciences, University of OsloBjørn Dalhus, Dept. Medical Biochemistry, Univ. of Oslo and Oslo Univ. HospitalRalph Dollner, Department of Otorhinolaryngology, Head and Neck Surgery, Oslo University HospitalTerje Espevik, Norwegian University of Science and Technology, TrondheimPeter Gaustad, Dept. of Medical Microbiology, University of Oslo and Oslo University HospitalTobias Gedde-Dahl, Dept. of Haematology, Oslo University HospitalEinar Gran, Lovisenberg Hospital, OsloHarleen Grewal, Gades Institute, University of Bergen and Haukeland University HospitalKrzysztof Grzyb, Dept. of Pathology, Oslo University HospitalGuttorm Haraldsen, Dept. of Pathology, University of Oslo and Oslo University HospitalAre Holm, Dept. of Respiratory Medicine, Oslo University Hospital Harald Holte, Dept. of Oncology, Oslo University HospitalJørgen Jahnsen, Department of Medicine, Akershus University HospitalKjetill S. Jacobsen, Centre for Ecological and Evolutionary Synthesis, University of OsloKnut-Dahl Jørgensen, Dept. of Pediatrics, Oslo University HospitalMari Kaarbø, Dept. of Microbiology, University of Oslo and Oslo University HospitalBenedicte A. Lie, Dept. of Medical Genetics, Oslo University HospitalFridtjof Lund-Johansen, Dept. of Immunology, Oslo University HospitalTrond Leren, Dept. of Medical Genetics, Oslo University HospitalTerje E. Michaelsen, School of Pharmacy, Dept. of Pharmaceutical Chemistry, University of OsloKarsten Midtvedt, Dept. of Internal Medicine, Oslo University HospitalTom Eirik Mollnes, Dept. of Immunology, University of OsloJ. Preben Morth, Centre for Molecular Medicine, University of OsloJohanna Olweus, Institute for Cancer Research, Oslo University Hospital

Peng Lei RCN UiOElin Bergseng RCN UiOJorunn Stamnæs ERC UiOSiri Dørum RCN-CIR UiOFleur du Pre S-EN RHA OUSOmri Snir ERC/S-EN RHA UiOBishnuedo Roy ERC UiOXi Chen S-EN RHA OUSRasmus Iversen ERC UiOBritt Nakken S-EN RHA OUSAstrid E. V. Tutturen RCN-CIR UiO

PHD STUDENTS Name Funding* Employer*Henrik Aamodt OUS OUSKristin Aas-Hanssen RCN/S-EN RHA UiOAxel Berg-Larsen UiO UiOMalin C. Bern RCN UiOAnna Bujko S-EN RHA OUSInês Cardoso EU UiOAsbjørn Christophersen S-EN RHA/ImmusanT/RCN UiO /OUSMarita Borg Distefano UiO UiOStian Foss UiO UiOIbon Eguiluz Gracia S-EN RHA OUSAlgirdas Grevys UiO UiOKathrin Hnida EU UiOChristina Hoffmann RCN-CIR UiOLene Støkken Høydahl RCN UiOShiva Dahal Koirala RCN-CIR UiODorota Joanna Konorska RCN-CIR UiOAna Kucera UiO UiODuarte Nunes De C Mateus UiO UiOGuro Reinholt Melum S-EN RHA OUSNadia Mensali OUS/UiO UiOElisabeth Müller UiO UiOJeannette Nilsen RCN OUSNicolay Rustad Nilssen S-EN RHA OUSAnna Parente Ribes NCS/UiO UiOLouise Risnes S-EN RHA OUSKine Marita K. Sand UiO UiOVikas K. Sarna S-EN RHA OUSFredrik Hellem Schesvold NCS OUS Øyvind Steinsbø UEG/S-EN RHA/OUS UiO /OUS

STUDENTSName StudyAstri Frafjord MScShuai Guo MScHeidi Anine Korsmo MScÁlvaro Sahún Español BScBranislava Stankovic MScMerete Storflor MScSanjib Halder MScMelanie Manzke MScMartine Schrøder MSc

Name StudyMira Halvorsen Børstad MScNora Valeur MScSofie Navelsaker MScHanna Noordzij MScIna Hodnebrug MScRahel Frick MScHeidrun Elisabeth Lode MScCamilla Myklebust MScSowmya Subbana MSc

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Norbert Roos, Dept. of Molecular Biosciences, University of OsloAnne Simonsen, Institute of Basic Medical Sciences, University of Oslo Ingebjørg Skrindo, Department of Otorhinolaryngology, AhusAnne Spurkland, Institute of Basic Medical Sciences, University of OsloHarald Stenmark, Centre for Cancer Biomedicine, Univ. of Oslo and Oslo Univ. HospitalBernt Thiede, Biotechnology Center, University of OsloGeir Tjønnfjord, Dept. of Haematology, Oslo University HospitalSheraz Yaqub, Dept. of Surgery, Oslo University HospitalEinar-Martin Aandahl, Dept. of Surgery, Oslo University HospitalOle Øyen, Dept. of Surgery, Oslo University HospitalResearchers at Nextera AS, Oslo Innovation Centre

INTERNATIONALWilliam Agace, Lund University, SEChristian Brix Andersen, Aarhus University, DKFrancesco Annunziato, University of Florence, ITRichard S. Blumberg, Harvard Medical School, USKurt Bommert, University of Würzburg, DEAnthony Bosco, Telethon Institute of Child Health Research, AUCecilia Bucci, University of Salento, ITSøren Buus, University of Copenhagen, DKJo Caers, Centre Hospitalier Universitaire de Liège, BEJason Cameron, Novozymes Biopharma Ltd., UKInhak Choi, University of Busan, KRMatthew Collin, Institute of Cellular Medicine, Newcastle UniversityShaodong Dai, National Jewish Health, USMarc Dalod, Centre d’Immunologie de Marseille-Luminy FRMorten Dziegiel, Rigshospitalet – Copenhagen University Hospital, DKTatiana Efimova, Washington University School of Medicine, USCaroline Ekblad, Affibody AB, SEPeter M. Elias, University of California San Francisco, USLaszlo Fesus, University of Debrecen, HUMattias Forsell, Karolinska Institutet, SEDonald Forthal, University of California, California, USJohan Garssen, University of Utrecht and Danone Research Centre for Specialised Nutrition, NLGeorg Georgiou, University of Texas, USMariano Grasselli, Universidad Nacional de Quilmes-IMBICE, AR

Patrick Holt, Telethon Institute of Child Health Research, AUAnn Hosmalin, Cochin Institute, FR Bertrand Huard, University of Geneva, CHBana Jabri, University of Chicago, USLeo C. James, Medical Research Council Laboratory of Molecular Biology, UKFranziska Jundt, Charite – Universitätsmedizin BerlinDE Thomas J.D. Jørgensen, University of Southern Denmark, DKJohn Kappler, National Jewish Health, USChaitan Khosla, Stanford University, USChu-Young Kim, National University of Singapore, SIFrits Koning, Leiden University Medical Center, NLWayne Lencer, Harvard Medical School, USAna-Maria Lennon-Dumenil, Institut Curie, Paris, FR Wiebke Ludwig-Peitsch, Klinik für Dermatologie, DEBernard Malissen, Centre d’Immunologie de Marseille-Luminy, FRKristiina Malmstrøm, Helsinki University, FIRudolf Manz, University of Lubeck, DEMarkku Mäki, University of Tampere, FIJeffery Miner, Washington University School of Medicine, USJacques Neefjes, Netherlands Cancer Institute, NLMorten Nielsen, Technical University of Denmark, DKMorten S. Nielsen, University of Aarhus, DKHugh Thomson Reyburn, Spanish National Center for Biotechnology, ESPaul Roche, NIH, USDerry C. Roopenian, The Jackson Laboratory, USDaniele Sblattero, University of Piemonte, ITHauke Smidt, Wageningen University, NLDimitri Svergun, European Molecular Biology Laboratory, DEMario Vaz, St. Johns Research Institute, INGestur Vidarsson, Sanquin Research, University of Amsterdam, NLPatrick C. Wilson, University of Chicago, USCisca Wijmenga, University Medical Center Groningen, NLJenny Woof, University of Dundee, UKAnna Wu, University of California Los Angeles, USKai W. Wucherpfennig, Dana-Farber Cancer Institute, USHideo Yagita, Jutendo University, JPGur Yaari, Bar-Ilan University , ISDov Zipori, Weizmann Institute, IS


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MSCIn 2014, 5 CIR master students graduated from the University of Oslo. Two foreign students performed their work for MSc degree at CIR and graduated in Italy and Netherland respectively.Jeanette NilsenAstri FrafjordHeidi Anine KorsmoMira Halvorsen BørstadMartin Mc AdamJeta Sadikaj Brenda van Dieren

Álvaro Sahún Español did a project at CIR for a BSc degree in Spain.

GENDER EQUALITY PROGRAMAt CIR and generally in molecular bio-medical research there is a high proportion of female PhD students and postdocs, while the majority of the senior scientists and group leaders are male. CIR and the University of Oslo value gender diversity and aim to increase the number of female researchers in senior scientist positions. Women, more so than men, leave academ-ia during their postdoctoral engagements and transition to independent researchers. CIR acknowledges that the centre, our host institution and other academic institutions nationally and abroad are at risk of losing many talents, possessing valuable and highly specialised competency.

In 2013, in line with the gender diversity strategy of the University of Oslo, CIR pro-vided two development grants to support the career of female scientists. CIR has obtained earmarked funding from the Research Council of Norway (RCN) to

PHDA large number of PhD students have graduated from CIR. The ambition has been to educate 35 new PhDs during this 10 years period. A total of 33 PhD students have already successfully defended their thesis so this goal is almost achieved. In 2014, two female students defended their thesis:

ASTRID ELISABETH VOORHAM TUTTUREN, “Enrichment and identification of citrul-linated proteins in biological samples”. Supervisor: Ludvig M. Sollid.

SYNNE JENUM, “Mycobacterium tubercu-losis infection and disease – a contribution to the understanding of immunological diagnostics in children”. Supervisor: Frode Jahnsen.

EDUCATION AND CAREERDEVELOPMENT

COMPLETED PHD DEGREES AT CIR PER YEAR FROM 2008 TO 2014

20142008 2009 2010 2011 2012 2013

8

7

6

5

4

3

2

1

0

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launch this program. Following an evaluation of applicants by the centre’s scientific advisory board, financial support was granted for two years to two selected talents.

This has been a big success. The candidates either received career grants for 2015 or scored at the top range in the evaluation of their applications.

The gender equality program will be con-tinued in 2015 and 2016 and the new career development grants for female scientists were announced in the end of 2014.

CAREER DEVELOPMENT AND OPPORTUNITIESCIR continues to support the career develop-ment of our talents. In 2014 the Medical Faculty has through the “phasing in scheme” announced an associate professor-ship for a junior faculty member within CIR. The selection board has now submitted their recommendation, and we hope the position will be filled before the summer of 2015.

Two young CIR scientists, Cinzia Progida and Anders Tveita, received career grants from the Norwegian Cancer Society and Progida also received a “Young researcher career grant” from the Research Council of Norway.

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ACTIVITIE40


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S

One of the core activities at CIR is the Visit-ing Professor program. CIR scientists have an extensive international network which has made it possible to attract some of the world’s most important scientists in medi-cal sciences to Oslo. The invited professors stay for one week at CIR. During this week they engage in scientific discussions with researchers, supervision of CIR students and give two public lectures for the whole scientific environment at the University of Oslo and the Oslo University hospital. These visits have resulted in fruitful collaborations resulting in joint publications, researcher mobility and new ideas. A total of twelve professors have been included in the Visit-ing Professor program, and many of them have visited us twice.

In 2014, Susan K. Pierce (NIAID, NIH, USA) revisited CIR for her second time in June and Mark M. Davis (Stanford University, USA) joined the Visiting Professor program in August.

We are very pleased to announce that Mark M. Davis and Bana Jabri (University of Chicago, USA) will revisit CIR in 2015, and Bernhard Malissen (Centre d’Immunologie de Marseilles-Luminy, France) will join the Visiting Professor faculty in 2015 and has accepted to visit CIR in June. We are very much looking forward to their visits.New Visiting Professors are nominated by CIR staff and will be invited to CIR in the future.

SUSAN K. PIERCEDr. Pierce works at the National Institute of Allergy and Infectious Diseases, NIH, US. Pierce focuses her work on B-cell receptor signaling and trafficking as well as on the acquisition and maintenance of immuno-logical memory in B cells. Her group studies the regulation of these processes during immune responses to infections and vac-cination and has a special interest in the immunological memory response to the malaria parasite. During her visit in June, Pierce gave two guest lectures entitled “Regulating the initiation of antigen-driven B cell responses" and “The acquisition of immunity in malaria”.

MARK M. DAVISDr. Davis works at the Stanford University in California, US. His focus is to understand the characteristics of a healthy humane im-mune system. Davis and his research group are trying to define what a normal immune response look like at the molecular and cellular level. There is no easy test to look for normal function of a patient’s immune system, and one goal of Davis’ research is to generate a simple battery of tests to be performed on a blood sample that can give information about the health status of your complex immune system. The future aim is to be able to give optimal treatment to patients and customized vaccines to older people. During his visit at CIR in August, Davis gave two lectures. One was entitled “Immunology taught by humans” and the other was part of a minisymposium on T cells in health and disease and was entitled “Molecular aspects of T cell recognition and applications to human responses”.

MINI-SYMPOSIUMT CELLS IN HEALTH AND DISEASE / AUG 27Contributors and titles:Mark M. Davis, Stanford University, USA. “Molecular aspects of T cell recognition and applications to human responses”.

Yueh-Hsiu Chien, Stanford University, USA. “Gamma delta T cells: First line of defense and beyond”.

Shuo-Wang Qiao, Centre for Immune Regulation, University of Oslo. “The CD4+ T-cell response to gluten in celiac disease.

Geir Åge Løset, Centre for Immune Regula-tion, University of Oslo and Nextera AS. “CD4+ TH-cell epitope discovery using MHC class II displayed on filamentous bacterio-phages”.

VISITING PROFESSOR PROGRAM

Susan K. Pierce

Mark M. Davis

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WORK PACKAGE (WP) SYMPOSIA In CIRs research plan for the last five years (2013-2017) we introduced a new strategy to enhance scientific interaction between the research groups. Projects were organized into four work packages (WP) with common research focus. The WPs bridge disease models and cross lab-boundaries and will hopefully enhance sharing of knowledge and skills between the scientists and students. The four main themes for the WPs are:WP1 – Function of APCs in autoimmunity and allergyWP2 – T-cell repertoire in autoimmunity and allergyWP3 – Pathogenic T-B collaborationWP4 – Pathogenic and regulatory antibodies

WP1 SYMPOSIUM / MAY 27Goal: Establishment of a competence/ technology “database”.Program: Introduction by the WP coordinator Espen S. Bækkevold, short presentations by attendees, and discussion of future WP-activities.

WP4 SYMPOSIUM / OCT 16Title: Generation of recombinant antibodies and derived fragments Program: Introduction by the WP coordinator Jan Terje Andersen.

Stian Foss: “Antibody production using the HEK293E cell line”

Bjørg Simonsen: “Antibody production using the HEK293E/F cell lines”

Xi Chen: “Eukaryotic expression of antibody fragments and characterization”

Kristin S. Gunnarsen/Lene Støkken Høydahl: “Prokaryotic expression of antibody fragments and characterization”

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GUEST LECTURESCIR organizes a series of guest lectures. Most lectures are hosted by a postdoc invitation committee. The 2014 committee consisted of Omri Snir, Lisa M. Gruber, Cinzia Progida, Kristin S. Gunnarsen and Peter C. Huszthy.

IN 2014, CIR ORGANIZED 8 GUEST LECTURES:Jacques Neefjes, a former member of the CIR Visiting Professor faculty from the Netherlands Cancer Institute in Amsterdam, visited us in June and gave a lecture entitled "How Salmonella causes cancer and the epidemics of gallbladder carcinoma in India". Professor Neefjes is a cell biologist who has made large contributions to the detailed understanding of antigen presenta-tions by MHC molecules.

Kunchithapadam Swaminathan visited CIR in June and gave a lecture entitled “Happy marriages among biophysical tech-niques”. Professor Swaminathan is a struc-tural biologist which heads a research group at the National University of Singapore. His research is focused on cell signaling and gene regulation in human diseases and in his talk he introduced us to the strength and limitations to some of the contemporary biophysical techniques.

Matthew Collin visited CIR in June and gave a lecture entitled “Human dendritic cells in health and disease”. Professor Collin heads a research group at the Newcastle Univer-sity and the Director of adult bone marrow transplantation at the Northern Centre for bone marrow transplantation. The focus of his research is to understand the origin and function of human dendritic cells.

Patrick Holt visited CIR in June and gave a lecture entitled "Treg-mediated control of IgE-mediated acute phase responses??”. Professor Holt is the head of the Division of Cell Biology at the Telethon Institute and University of Western Australia in Perth, and heads a research group with focus on the pediatric immune system in relation to asthma and allergy.

Ralf Küppers visited CIR in September and gave a lecture entitled “Generation and function of human memory B cells and

aspects of CLL pathogenesis”. Professor Küppers heads a research group at the Institute of Cell Biology (Cancer Research) at University of Duisburg-Essen in Essen, Germany. Their research aims at under-standing the pathogenesis of B cell tumors by comparing the gene expression profile of the B cell lymphomas or leukemias with the B cell subsets they originate from.

Ana-Maria Lennon-Dumenil visited CIR in October and gave a lecture entitled “Coordinating cell migration with function: the example of dendritic cells”. Dr. Lennon- Dumenil heads a research group at the Institut Curie in Paris, France, which aims to identify the molecular mechanisms involved in the space and time-related control of the function of antigen-presenting cells.

Gur Yaari visited CIR in November and gave a lecture entitled: “Mining B cell repertoire dynamics from next-generation sequencing studies”. Dr. Yaari heads a research group at the Bar-Ilan University in Israel which develops computational and statistical tools to process and analyze high-throughput biological data in order to obtain meaningful biological insights into the adaptive immune system.

Gabriel D. Victora visited CIR in December and gave a lecture entitled: “Darwin in miniature: antibody evolution in germinal centers”. Dr. Victora is a young scientist from the Whitehead Institute for Biomedical Research, MIT, Cambridge, MA, US. He pre-sented several cutting edge techniques used in his laboratory to study the generation of germinal centers in lymph nodes. His studies are important to understand the dynamics and regulation of germinal center B cells and have implications for how vac-cines work, but also for the development of allergies, autoimmune diseases and lymphomas.

In collaboration with the KG Jebsen Centre for Research on Influenza Vaccines (JIV) and Norwegian Society for Immunology (NSI) we arranged a guest lecture by:

Simon J. Draper from the Blood-Stage Malaria Group Jenner Institute at the University of Oxford, UK. Title: “Develop-ment of broadly-neutralising vaccines against the blood-stage infection of human malaria”.

Ana-Maria Lennon-Dumenil

Gabriel D. Victora

Gur Yaari

Matthew Collin

Ralf Küppers

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INTERNAL ACTIVITIESPROJECT MEETINGSOnce a month, all CIR members partici-pates in a project meeting where research projects are presented to other colleagues within CIR. This is a great opportunity to have scientific discussions, critical review of recent data, and initiate new collaborations. It also provides a friendly venue where less experienced junior scientists can practice presentation of experimental data. The pro-ject meeting is one of the key events which gather all CIR members, and it is important for building centre identity. After the project presentation pizza and soft drinks are served, and the scientific discussions continue in a more relaxed atmosphere.

RETREATAugust 18-19 2014, CIR arranged a retreat to Soria Moria in Oslo. A total of 80 people attended the conference. Attendants were the members of CIR and the scientific advi-sory board. Members of the CIR centre board were also present during parts of the pro-gram. Two international keynote speakers were invited. Rudolf Valenta (Medical Uni-versity of Vienna) presented “From allergen genes to new forms of diagnosis and therapy of allergy”, and Rikard Holmdahl (Karolinska Institutet, Stockholm), member of the CIR scientific advisory board, gave a talk entitled “From genes to oxidation inflammation path-ways”. The talks of the keynote speakers were excellent and were followed by 15 very good selected oral presentations and 23 poster presentations by young CIR scientists. The program was divided into seven sessions which were chaired by researchers at CIR: Keynote lectures (Wang Dong and Alexandre Corthay), “Immune cells and their responses in the gut” (Inger Øynebråten), “T and B cells and extracellular molecules in celiac disease” (Anders Tveita), “Protein engineering and approaches to regulate immune responses” (Shuo-Wang Qiao), “Immune cells and responses in tumor pathogenesis” Espen Bækkevold), and “Anti-tumor responses, and “Transport and signalling pathways” (Jan Terje Andersen). The organizing com-mittee did an excellent job and consisted of Wang Dong, Fleur De Pré, Marte Hotvedt Hauskanger, Ibon Eguiluz Gracia, Elisabeth Müller, Nicolay Rustad Nilssen and Anders Sandvik.


August 18–19, 2014Soria Moria Hotel, Oslo

This material is confidential and is only for internal use at the Centre for Immune Regulation

CIR Retreat 2014

Program and abstracts

CIR_Abstract_book_2014.indd 1

12.08.14 11:22

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PUBLICATIONS46



IONS47


PAPERS IN SCIENTIFIC JOURNALSAas-Hanssen K, Funderud A, Thompson KM, Bogen B, Munthe LA (2014) Idiotype-specific Th cells support oligoclonal expansion of anti-dsDNA B cells in mice with lupus. J Immunol, 193 (6), 2691-8

Amundsen SS, Viken MK, Sollid LM, Lie BA (2014) Coeliac disease-associated polymor-phisms influence thymic gene expression. Genes Immun, 15 (6), 355-60

Andersen JT, Dalhus B, Viuff D, Ravn BT, Gunnarsen KS, Plumridge A, Bunting K, Antunes F, Williamson R, Athwal S, Allan E, Evans L, Bjørås M, Kjærulff S, Sleep D, Sandlie I, Cameron J (2014) Extending serum half-life of albumin by engineering neonatal Fc receptor (FcRn) binding. J Biol Chem, 289 (19), 13492-502

Bagherifam S, Skjeldal FM, Griffiths G, Mælandsmo GM, Engebråten O, Nyström B, Hasirci V, Hasirci N (2014) pH-Responsive Nano Carriers for Doxorubicin Delivery. Pharm Res. Oct 7.

Bakke O, Progida C. (2014). Emerging regula-tors of endosomal dynamics during mitosis. Cell Cycle.13(3):, 349-50

Bazso A, Bazso T, Szodoray P, Poor G, Kiss E (2014) Aseptic necrosis at multiple localisations in a lupus patient with lymphoma. Osteoporo-sis international: a journal established as result of cooperation between the European Founda-tion for Osteoporosis and the National Osteo-porosis Foundation of the USA 25:1415-1417.

Binsfeld M, Beguin Y, Belle L, Otjacques E, Hannon M, Briquet A, Heusschen R, Drion P, Zilberberg J, Bogen B, Baron F, Caers J (2014) Establishment of a murine graft-versus-mye-loma model using allogeneic stem cell trans-plantation. PLoS One, 9 (11), e113764

Bodolay E, Prohaszka Z, Paragh G, Csipo I, Nagy G, Laczik R, Demeter N, Zold E, Nakken B, Szegedi G, Szodoray P (2014) Increased lev-els of anti-heat-shock protein 60 (anti-Hsp60) indicate endothelial dysfunction, atheroscle-rosis and cardiovascular diseases in patients with mixed connective tissue disease. Immu-nologic research 60:50-59.

Borg M, Bakke O, Progida C (2014) A novel interaction between Rab7b and actomyosin reveals a dual role in intracellular transport and cell migration. J Cell Sci, 127 (22), 4927-39

Christophersen A, Ráki M, Bergseng E, Lundin KE, Jahnsen J, Sollid LM, Qiao SW (2014) Te-tramer-visualized gluten-specific CD4+ T cells in blood as a potential diagnostic marker for coeliac disease without oral gluten challenge. United European Gastroenterol J, 2 (4), 268-78

Corthay A (2014) Does the immune system naturally protect against cancer? Front Immunol, 5, 197

De Luca M, Cogli L, Progida C, Nisi V, Pasco-lutti R, Sigismund S, Di Fiore PP, Bucci C (2014) RILP regulates vacuolar ATPase through inter-action with the V1G1 subunit. J Cell Sci. 127(Pt 12), 2697-708.

Dhanasekaran S, Jenum S, Stavrum R, Ritz C, Kenneth J, Vaz M, Doherty TM, Grewal HM, TB Trials Study Group (Jahnsen FL)(2014) Concordant or discordant results by the tuber-culin skin test and the quantiFERON-TB test in children reflect immune biomarker profiles. Genes Immun, 15 (5), 265-74

Dhanasekaran S, Jenum S, Stavrum R, Wiker HG, Kenneth J, Vaz M, Doherty TM, Grewal HM, TB Trials Study Group (2014) Effect of non-tuberculous Mycobacteria on host biomarkers potentially relevant for tubercu-losis management. PLoS Negl Trop Dis, 8 (10), e3243

Dørum S, Bodd M, Fallang LE, Bergseng E, Christophersen A, Johannesen MK, Qiao SW, Stamnaes J, de Souza GA, Sollid LM (2014) HLA-DQ molecules as affinity matrix for iden-tification of gluten T cell epitopes. J Immunol, 193 (9), 4497-506

Etokebe GE, Bulat-Kardum L, Munthe LA, Balen S, Dembic Z (2014) Association of variable number of tandem repeats in the coding region of the FAM46A gene, FAM46A rs11040 SNP and BAG6 rs3117582 SNP with susceptibility to tuberculosis. PLoS One. Mar 13;9(3):e91385.

Fenaroli F, Westmoreland D, Benjaminsen J, Kolstad T, Skjeldal FM, Meijer AH, van der Vaart M, Ulanova L, Roos N, Nyström B, Hil-dahl J, Griffiths G. Nanoparticles as drug de-livery system against tuberculosis in zebrafish

Cover page from Borg et al. 2014, Journal of Cellular Science, 127 (22), 4927-4939. Reproduced with permission.

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embryos: direct visualization and treatment (2014) ACS Nano, Jul 22;8(7):7014-26.

Haabeth OA, Tveita AA, Fauskanger M, Schjesvold F, Lorvik KB, Hofgaard PO, Omholt H, Munthe LA, Dembic Z, Corthay A, Bogen B (2014) How Do CD4(+) T Cells Detect and Eliminate Tumor Cells That Either Lack or Express MHC Class II Molecules? Front Immunol, 5, 174

Hjelle AM, Apalset E, Mielnik P, Bollerslev J, Lundin KE, Tell GS (2014) Celiac disease and risk of fracture in adults--a review. Osteo-poros Int, 25 (6), 1667-76

Iversen R, Mysling S, Hnida K, Jørgensen TJ, Sollid LM (2014) Activity-regulating struc-tural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange. Proc Natl Acad Sci U S A, 111 (48), 17146-51

Jabri B, Chen X, Sollid LM (2014) How T cells taste gluten in celiac disease. Nat Struct Mol Biol, 21 (5), 429-31

Jacobsen J, Haabeth OA, Tveita AA, Schjetne KW, Munthe LA, Bogen B (2014) Naive idiotope-specific B and T cells collaborate efficiently in the absence of dendritic cells. J Immunol, 192 (9), 4174-83

Jenum S, Grewal HM, Hokey DA, Kenneth J, Vaz M, Doherty TM, Jahnsen FL, TB Tri-als Study Group (2014) The frequencies of IFNγ+IL2+TNFγ+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® gold in-tube response in a prospective study of healthy indian adoles-cents. PLoS One, 9 (7), e101224

Knudsen Sand KM, Landsverk OJ, Berg-Larsen A, Bakke O, Gregers TF (2014) The human-specific invariant chain isoform Iip35 modu-lates Iip33 trafficking and function. Immunol Cell Biol, 92 (9), 791-8

Laczik R, Soltesz P, Szodoray P, Szekanecz Z, Kerekes G, Paragh G, Rajnavolgyi E, Abel G, Szegedi G, Bodolay E (2014) Impaired endo-thelial function in patients with undifferen-tiated connective tissue disease: a follow-up study. Rheumatology 53:2035-2043.

Lin M, Du L, Brandtzaeg P, Pan-Hammarström Q (2014) IgA subclass switch recombination in human mucosal and systemic immune com-partments. Mucosal Immunol 7 (3), 511-20

Lundin KE (2014) Non-celiac gluten sensitivity - why worry? BMC Med, 12, 86

Makharia GK, Mulder CJ, Goh KL, Ahuja V, Bai JC, Catassi C, Green PH, Gupta SD, Lundin KE, Ramakrishna BS, Rawat R, Sharma H, Sood A, Watanabe C, Gibson PR, World Gastroen-terology Organization-Asia Pacific Associa-tion of Gastroenterology Working Party on Celiac Disease (2014) Issues associated with the emergence of coeliac disease in the Asia–Pacific region: a working party report of the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology. J Gastroenterol Hepatol, 29 (4), 666-77

Melum GR, Farkas L, Scheel C, Van Dieren B, Gran E, Liu YJ, Johansen FE, Jahnsen FL, Baekkevold ES (2014) A thymic stromal lymphopoietin-responsive dendritic cell sub-set mediates allergic responses in the upper airway mucosa. J Allergy Clin Immunol, 134 (3), 613-621.e7

Nakken B, Bodolay E, Szodoray P (2014). Cytokine Milieu in Undifferentiated Connec-tive Tissue Disease: a Comprehensive Review. Clinical reviews in allergy & immunology

Rahman MA, Kristiansen PE, Veiseth SV, Andersen JT, Yap KL, Zhou MM, Sandlie I, Thorstensen T, Aalen RB (2014) The arabidop-sis histone methyltransferase SUVR4 binds ubiquitin via a domain with a four-helix bun-dle structure. Biochemistry, 53 (13), 2091-100

Sand KM, Bern M, Nilsen J, Dalhus B, Gunnar-sen KS, Cameron J, Grevys A, Bunting K, Sandlie I, Andersen JT (2014) Interaction with Both Domain I and III of Albumin Is Required for Optimal pH-dependent Binding to the Neonatal Fc Receptor (FcRn). J Biol Chem, 289 (50), 34583-94

Sand KM, Dalhus B, Christianson GJ, Bern M, Foss S, Cameron J, Sleep D, Bjørås M, Roopenian DC, Sandlie I, Andersen JT (2014) Dissection of the neonatal Fc receptor (FcRn)-albumin interface using mutagenesis and anti-FcRn albumin-blocking antibodies. J Biol Chem, 289 (24), 17228-39

Schwarzer R, Nickel N, Godau J, Willie BM, Duda GN, Schwarzer R, Cirovic B, Leutz A, Manz R, Bogen B, Dörken B, Jundt F (2014) Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model. Blood Cancer J, 4, e217

Cover from Proc Natl Acad Sci U S A, 111 (48). Repro-duced with permission

Cover from Nature Structural & Molecular Biology, Volume 21 No 5. Reproduced with permission

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Senolt L, Grassi W, Szodoray P (2014) Labora-tory biomarkers or imaging in the diagnostics of rheumatoid arthritis? BMC medicine 12:49.

Skrede S, Steinsland H, Sommerfelt H, Aase A, Brandtzaeg P, Langeland N, Cox RJ, Saevik M, Wallevik M, Skutlaberg DH, Tellevik MG, Sack DA, Nataro JP, Guttormsen AB (2014) Experimental infection of healthy volunteers with enterotoxigenic Escherichia coli wild-type strain TW10598 in a hospital ward. BMC Infect Dis, 14, 482

Solberg LB, Brorson SH, Stordalen GA, Bækkevold ES, Andersson G, Reinholt FP (2014) Increased tartrate-resistant Acid phosphatase expression in osteoblasts and osteocytes in experimental osteoporosis in rats. Calcif Tissue Int 94 (5), 510-21

Sollid LM, Pos W, Wucherpfennig KW (2014) Molecular mechanisms for contribution of MHC molecules to autoimmune diseases. Curr Opin Immunol, 31C, 24-30

Steinsbø Ø, Henry Dunand CJ, Huang M, Mesin L, Salgado-Ferrer M, Lundin KE, Jahn-sen J, Wilson PC, Sollid LM (2014) Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells. Nat Commun, 5, 4041

Szodoray P, Hajas A, Toth L, Szakall S, Nakken B, Soltesz P, Bodolay E (2014) The beneficial effect of plasmapheresis in mixed connective tissue disease with coexisting antiphospho-lipid syndrome. Lupus 23:1079-1084.

Toft-Hansen H, Rasmussen KS, Staal A, Roggen EL, Sollid LM, Lillevang ST, Barington T, Husby S (2014) Treatment of both native and deamidated gluten peptides with an en-do-peptidase from Aspergillus niger prevents stimulation of gut-derived gluten-reactive T cells from either children or adults with celiac disease. Clin Immunol, 153 (2), 323-31

Tutturen AE, Fleckenstein B, de Souza GA (2014) Assessing the citrullinome in rheuma-toid arthritis synovial fluid with and without enrichment of citrullinated peptides. J Pro-teome Res, 13 (6), 2867-73

Tveita AA, Haabeth OA, Bogen B (2014) Limitations of bystander killing in Th1/M1 immune responses against a secreted tumor antigen. OncoImmunology, 3 (9), e954953

Tveita AA, Schjesvold FH, Sundnes O, Haabeth OA, Haraldsen G, Bogen B (2014) Indirect CD4+ T-cell-mediated elimination of MHC II(NEG) tumor cells is spatially restrict-ed and fails to prevent escape of antigen-neg-ative cells. Eur J Immunol, 44 (9), 2625-37

Vincze M, Der H, Kerekes G, Szodoray P, Zeher M, Danko K, Soltesz P (2014) De-creased flow-mediated dilatation with increased arterial stiffness and thickness as early signs of atherosclerosis in polymyositis and dermatomyositis patients. Clinical rheu-matology 33:1635-1641.

Wong D, Winter O, Hartig C, Siebels S, Szyska M, Tiburzy B, Meng L, Kulkarni U, Fähnrich A, Bommert K, Bargou R, Berek C, Chu VT, Bogen B, Jundt F, Manz RA (2014) Eosinophils and megakaryocytes support the early growth of murine MOPC315 myeloma cells in their bone marrow niches. PLoS One, 9 (10), e109018

Zold E, Bodolay E, Dezso B, Soos G, Nakken B, and Szodoray P (2014) Mixed connective tissue disease associated with autoimmune hepatitis and pulmonary fibrosis. The Israel Medical Association journal: IMAJ 16:733-734.

OTHER PAPERSMoum B, Lundin KE (2014) Biosimilar medicines in inflammatory bowel disease. Tidsskr Nor Laegeforen, 134 (8), 819-20

Frich J, Lundin KE, Os I (2014) [The grading system--balancing various interests] Tidsskr Nor Laegeforen, 134 (1), 14-5

Frich J, Lundin KE, Os I (2014) [J. Frich and colleagues reply] Tidsskr Nor Laegeforen, 134 (5), 496; discussion 497

BOOKS AND BOOK CHAPTERSAndersen J.T., Hjelstuen O.K. and Sandlie I. Medical technology - meeting tomorrow’s healthcare challenges, edited by John Grue and Anne-Brit Kolstø. Chapter: From basic research to innovation. Novus forlag, 2014. (ISBN 978-82-7099-791-6).

Brandtzaeg P, Eskeland S. Bevisvurdering og juss eller “vitenskap og galskap”. s. 17-29. I:

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Festskrift til Fredrik Fasting Torgersen (Red.: Eskeland KO, Mossig H, Os Simonsen Ø, Steen T, Holck P). SpreDet Forlag, Oslo, 2014 (ISBN: 978-82-93277-13-2).

PATENTS Andersen JT and Sandlie I (with Novozymes): Albufuse2 Domain III extreme C-terminal (EP11164955.4).

Andersen JT and Sandlie I (with Novo-zymes): Albumin derivatives and variants (WO2011124718 A1).

Andersen JT and Sandlie I (with Novozymes): Albumin variants (EP10159450.5).

Andersen JT and Sandlie I (with Novozymes): Albumin variants (WO2011051489 A2).



Andersen JT and Sandlie I: Modulation of albumin half-life (EP9174698.2).

Andersen JT and Sandlie I (with Novozymes): Albufuse mutations (EP11164989.3).

Andersen JT and Sandlie I: Albumin combina-tion mutants (EP12177916.9 and EP12191859.9).

Andersen JT, Bern M and Sandlie I: Albumin variants fused to immunogens (AlbuVax) for improved transcellular delivery, US 61/936,442. Filed 06.02.2014

Bogen B and Braathen R: Heterodimeric vaccine molecules (U.S. Provisional Patent Application Serial No. 61/695,639).

Bogen B and Hofgaard PO: A novel mouse model for multiple myeloma (MOPC315.BM) that allows noninvasive spatiotemporal detec-tion of osteolytic disease (U.S. Provisional Patent Application Serial No. 61/708,310).

Bogen B, Fossum E and Grødeland G: Vacci-bodies targeted to cross-presenting dendritic cells (US serial no: 61538,186).

Di Niro R, Sollid LM and Wilson PC: Identifica-tion of antibodies in mucosal cells (US provi-sional, US61/352/467).

Dooper M, Myrset HR, Bogen B: New fusion proteins for the treatment of allergic diseases (US application/PCT international application no. 13/666,023, Canadian Patent Application No. 2,794,051).

Johansen FE, Sandvik A and Engstad RE: Methods of treating or preventing inflam-matory disease of the intestinal tract (PCT/GB2008/003850).

Løset GÅ and Sandlie I: Multivalent phage dis-play systems and methods (WO2011/036555).

Løset GÅ, Frigstad T, Sandlie I and Bogen B: Disulphide bond-stabilized functional soluble MHC class II heterodimers (WO2011/101681).

Løset GÅ: pVII phage display (WO2009/024591).

Løset GÅ: Signal sequence-independent pIX phage display (WO2010/097411).

Mollnes TE, Espevik T, Sandlie I, Gunnarsen JT, Lau C. A humanized antibody against CD14, PCT/US14/31402. Filed 21.03.2014,

Munthe LA, Carlsen H, Blomhoff R and Bogen B: Triple transgenic mouse model of autoim-mune disease and NF-kB in vivo imaging (US provisional, US61/262/968).

Reiersen H, Løset GÅ, Hagemann UB and Owen D: Method for screening phage display libraries against each other (WO2010/097589).

Ruffini PA, Fredriksen A and Bogen B: Homod-imeric protein constructs (WO2010/61358513, EP10167291.3).

Sandlie I, Andersen JT and Bern M: Albumin variants fused to immunogens (AlbuVax) for improved transcellular delivery (61033-13082-US-P).

Sandlie I, Andersen JT and Foss S: A human IgG1 mutant with improved binding to tri-partite motif-containing protein 21 (TRIM21) (61500-13035-US-P).

Sandlie I, Andersen JT and Sand KMK: Human albumin mutants with decreased binding to FcRn (2132-13083-US-P).

Sollid LM, Qiao SW, Christophersen A and Lundin KEA: Detection of gluten specific T cells (U.S. Provisional Patent Application Serial No. 61/823,072).

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DISSEMINATION53


INVITED LECTURESAndersen, JT. Life Science workshop at Oslo University Hospital, June 10, Oslo, Norway

Andersen, JT. CRS Workshop Albumin: The Next Generation Protein Therapeutic at the Controlled Release Society's Annual Meet-ing and Exposition in Chicago, July 13-16, Illinois, USA

Andersen, JT. Seminar October 21. Depart-ment of Microbiology, University of Oslo, Oslo University Hospital, Rikshospitalet, Norway

Andersen, JT: Intracellular antibody sensing in the battle against infection. Norwegian Society for Immunology 32nd annual meet-ing, November 13, Oslo, Norway

Bogen B:” How do CD4+ T cells eliminate tumor cells that lack MHC class II mole-cules? “. Norwegian Cancer Symposium, June 10-12, Oslo, Norway

Bogen B: “A Novel Mouse Model for Multiple Myeloma (MOPC315.BM)”. Department of Hematology, Mount Sinai Hospital/ Icahn School of Medicine, December 17, New York, USA

Brandtzæg P. NSI Honorary Member Lec-ture: “The advent of immunological research in Norway and NSI as a catalyst”. November 13, Oslo, Norway

Corthay A “What is inflammation? An immunologist’s perspective”. Norwegian Inflammation Network seminar “Sufficient options to treat inflammation? Looking at the pipeline of the pharmaceutical indus-try”, October 29, Oslo, Norway

Corthay A “Can tumor-specific Th2 cells be used to treat cancer?”. Norwegian Cancer Symposium 2014 – Harnessing Innate and Adaptive Immunity in Cancer Therapy, June 10-12, Oslo, Norway

Corthay A “Cancer prevention by the immune system: role of CD4+ T cells, macrophages, and interleukin-1”. 11th Inter-national Conference on Innate Immunity, June 1-6, Olympia, Greece

Koster G: “Membrane nanotube formation by proteins - regulation by force and cur-vature” University of California Berkeley. February 20, USA

Lundin KE: «Controversies about bio-similars». Annual GEDII meeting, January 17, Lisboa, Portugal

Lundin KE: «HLA tetramers in the diagnosis of CDV. Prolamin Working Group meeting, September 26, Nantes, France

Lundin KE: «Celiac disease. Lecture at Postgrauduate training programme»,22nd European Gastroenterology Week, October 18-22, Vienna, Austria

Lundin KE: «Round table discussion - Should asymptomatic CD patients be treated?». 22nd European Gastroenterology Week, October 18-22, Vienna, Austria

Lundin KE: «Celiac disease – state of the art and unmet clinical needs». Gastroenterologi i fokus. November 20, Stockholm, Sweden

Sandlie I: Half-life extension by albumin or Fc-fusion. Gordon Conference on Antibody Biology and Engineering, March 23-28, Tuscany, Italy

Sandlie I: Tailoring the Lifespan of Bio-pharmaceuticals by Targeting the Neonatal Fc Receptor (FcRn), KTH, Royal Institute of Technology, School of Biotechnology, May 23, Stockholm, Sweden

Sandlie I: New perspective on IgG function. December 15. Department of Pathophysiol-ogy, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria

Sandlie I: Fra Grunnforskning til Innovasjon. Det Norske Vitenskapsakademi (January 29) and Cutting Edge Konferansen Oslo Inno-vation Week October 10, Oslo, Norway

Sandlie I: Strategier for å bygge produktive fagmiljøer. Odontologisk fakultets strategi-seminar, April 9, Praha, Czech Republic

Sollid LM: «Antigen recognition (B and T cell mechanisms». JDRF/Wellcome Trust Frontier Meeting. Common Mechanisms of Autoimmune Diseases, January 27-28, London, UK

Alexandre Corthay

Jan Terje Andersen

54


Sollid LM: «Coeliac disease: Food hypersen-sitivity coupled with autoimmunity». 12th EAACI Immunology Winter School: Basic immunology research in allergy and clini-cal immunology. January 30-Feb 2, Poiana Brasov, Romania

Sollid LM: «Immunopathogenesis of celiac disease». Columbia University Conference: Development of Therapies for celiac disease, March 20-21, New York, USA

Sollid LM: « Celiac disease: Interplay of autoimmunity and food hypersensitivity». Stanford Institute of Immunity, Transplan-tation and Infection Special Seminar, April 2, Stanford, USA

Sollid LM: «Celiac disease: When food is the problem». Gordon Research Conference: Immunochemistry & Immunobiology, June 1-6, Newry, USA

Sollid LM: «Immune control of celiac disease». 42nd Annual Meeting of the Scandinavian Society of Immunology, June 11-14, Reykjavik, Iceland

Sollid LM: «Transglutaminase 2: auto-antibody target and generator of T-cell epitopes». Gordon Research Conference: Transglutaminases in Human Disease Processes, June 29-July 4, Barga, Italy

Sollid LM: «Small bowel, celiac disease and adaptive immunity». Falk Symposium no 193: Celiac Disease and other small bowel disorders, September 5-6, Amsterdam, the Netherlands

Sollid LM: «The antibody response of celiac disease». 18th Germinal Centre Conference, September 11-14, Uddevalla, Sweden

Sollid LM: «New insights into the pathogenesis of coeliac disease: Gluten- gene-environmental interactions». 22nd European Gastroenterology Week, October 18-22, Vienna, Austria

Sollid LM: «Triggers and Drivers of autoim-munity: Lessons from coeliac disease». 22nd European Gastroenterology Week, October 18-22, Vienna, Austria

ORAL PRESENTATIONSBakke, O. Invariant chain (Ii), a multifunc-tional molecule, its role in sorting and Ii as a vehicle for antigen loading onto MHC I and MHCII. 8th International Workshop on Anti-gen Processing and Presentation, June 10-13, Philadelphia, PA, USA

Bujko A: Monocytes differentiate into mac-rophages and lymph node-homing dendritic cells in human gut, World Immune Regula-tion Meeting VIII-2014, March 19-22, Davos, Switzerland (oral and poster presentation).

Bujko A: Monocytes differentiate into macrophages and lymph node-homing den-dritic cells in human gut, 13th International Symposium on Dendritic Cells, September 14-18, Tours, France

Bækkevold ES: Human airway mucosal DCs respond to TSLP and induce Th2 responses. 8th World Immune Regulation Meeting March 19-22, Davos, Switzerland

Bækkevold ES: Novel concepts to investigate immunopathology in organ rejection. Medi-sinsk fakultets 200-års jubileum, September 10, Oslo universitetssykehus Rikshospitalet, Oslo

Hnida K, Stamnaes J, Chen X, Iversen R and Sollid LM «Functional implications of celi-ac-autoantibodies-transglutaminase inter-actions». Gordon-Merck Research Seminar Antibody Biology & Engineering, March 22-23, Barga, Italy

Jenum S: Characterization of Mycobacte-rium Tuberculosis specific T cells – clues to protective immunity? Årsmøte, Norsk Flow-cytometri Forening, April 30, Norway

Koster G: “Forces of membrane nanotubes in vitro and in vivo – regulation by physical membrane properties” Norsk biofysikkmøte, March 6, Soria Moria, Oslo, Norway

Kucera A. “Invariant chain as a vaccina-tion vehicle for loading of MHC I”. Annual meeting, Norwegian Society of Immunology, November 13, Oslo, Norway

Stankovic B. “Immune Cell Composition in Human Non-Small Cell Lung Cancer”. Annual meeting, Norwegian Society of Immunology, November 13, Oslo, Norway

Espen Bækkevold

Kathrin Hnida

55


Steinsbø Ø. «Binding motifs of gluten-specif-ic antibodies from celiac disease patients». Annual meeting, Norwegian Society of Immunology, November 13, Oslo, Norway

Steinsbø Ø: «Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells”. Award for excellent article published first half of 2014 Oslo University Hospital November 21, Oslo, Norway

Wang, D: “Autologous bone marrow Th cells can support multiple myeloma cell prolif-eration in vitro and in vivo”. Annual Meet-ing of the Federation of Clinical Immunology Societies (FOCIS), June 25-28, Chicago, USA. (oral and poster presentation, poster prize winner)

POSTER PRESENTATIONSBorg M, Bakke O, Progida C: “A novel Rab- actomyosin interaction reveals a dual role in intracellular transport and cell migration”. 14th International Advanced Light Micro - scopy Meeting. May 20-23, Oslo, Norway

Borg M, Bakke O, Progida C,: “A novel interaction between Rab7b and actomyosin cytoskeleton reveals multiple functions in intracellular transport and cell migration”. 1st International Meeting “Building The Cell”. September 24-26, Paris, France

Cardoso I, Stamnaes J, Iversen R, Sollid LM. «TG2 interactions with extracellular ma-trix proteins as probed with celiac disease antibodies». Gordon Research Conference: Transglutaminases in Human Disease Processes, June 29-July 4, Barga, Italy

Eguíluz-Gracia I, Melum GR, Döllner R, Bækkevold ES, Jahnsen FL: Experimen-tally-induced early recruitment of CD14+ monocytes in human allergic rhinitis. EAACI Winter School on Basic Research in Allergy and Clinical Immunology, January 30- February 2, Poiana Brasov, Romania

Algirdas Grevys: Fc-engineering of human IgG1 for altered binding to the neonatal Fc receptor affects Fc effector functions. Gordon Research Conference (GRC), March 23-28, Lucca (Barga), Italy

Gruber LM: Human small intestinal SIR-Pa+CD103+ dendritic cells display putative immunoregulatory features. 13th Inter-national Symposium on Dendritic Cells, September 14-18, Tours, France

Gruber LM: Human small intestinal SIRPa+CD103+CD1a+ dendritic cells display putative immunoregulatory features. 32nd Annual Meeting of the Norwegian Society for Immunology, November 13, Oslo, Norway

Haugen LH, Skjeldal FM, Bergeland T, Bakke O. Growth factor-induced phosphoraylation of Eps15 and Hrs regulates their binding to endosomes and RTK degradation, European Light Microscopy Meeting, May, Oslo, Norway

Hnida K, Stamnaes J, Chen X, Iversen R and Sollid LM «Epitope-dependent effect of celiac anti-TG2 hmAbs on preventing TG2 oxida-tion». Gordon-Merck Research Seminar Anti-body Biology & Engineering, March 22-23 and Gordon Research Conference, Antibody Biology & Engineering, March 23-28, Barga, Italy

Hnida K, Chen X, Iversen R, Graewert MA, Svergun D and Sollid LM « Structural basis for antigen recognition of Transglutaminase 2 specific autoantibodies in celiac disease». Gordon Research Conference: Transglutami-nases in Human Disease Processes, June 29-July 4, Barga, Italy

Iversen R: «Gluten, antibodies and TG2: mechanisms for generation of autoantibod-ies in celiac disease». 18th Germinal Centre Conference, September 11-14, Uddevalla, Sweden

McAdam. M. Engineering of novel antibodies for targeted anti-viral therapy. Norwegian Society for Immunology annual meeting, November 13, Oslo, Norway

Nilsen J, Høydahl LS, Gunnarsen KS, Qiao SW, Sollid LM, Sandlie I, Løset GÅ. Affinity maturation of a T cell receptor by use of phage display and deep sequencing. Norwe-gian Biochemical Society Contact Meeting, January 23-26, Røros, Norway

Nilsen J, Sand KMK, Bern M, Dalhus B, Sandlie I, Andersen JT. The impact of albumin DI on FcRn cross-species binding. Norwegian Society for Immunology annual meeting, Nov 13, Oslo, Norway

Linda Haugen

Marita Borg Stefano

56


Progida C, Borg M, Koster G, Bakke O: “Rab7b at the intersection of intracellular trafficking and cell migration”. 9th EMBO/Annaberg Workshop “Protein and lipid function in secretion and endocytosis”. January 14-19, Goldegg am See, Austria

Progida C, Borg M, Bakke O: “Rab7b and the actomyosin cytoskeleton: novel roles in intracellular trafficking and cell migration”. Conference “The Dynamic Cell 2014”. September 4-7,Cambridge, UK

Snir O, Mesin L, Lundin KE, Yaari G and Sollid LM. «Analysis of celiac disease auto-reactive gut-plasma cells and their corre-sponding memory compartment in peripher-al blood using high-throughput sequencing». 18th Germinal Center Conference, September 11-14, Uddevalla, Sweden

Steinsbø Ø: «Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells». 18th Germinal Centre Conference, September 11-14, Uddevalla, Sweden

Wang D, Fløisand Y, Tveita A, Thoresen AS, Bürgler S, Parente-Ribes A, Hofgaard P, Bogen B, Tjønnfjord G, Dalgaard J, Munthe L. “Autologous bone marrow Th cells can sup-port multiple myeloma cell proliferation in vitro and in vivo”. 1st International Winter Symposium on Immunobiology: Metabolism, Cancer, Auto immunity and Drug Discovery, October, Seefeld, Austria

OTHERAndersen, JT. Chair for Gordon Research seminars (GRS), Gordon Research Confer-ence (GRC) pre-seminar for young investi-gators in Antibody Biology & Engineering: Next-Generation Antibodies: From Biology to Therapeutics, March 23-28, Renaissance Tuscany Il Ciocco Resort, Lucca (Barga), Italy

Bakke, O and research group. Main organ-izer of 14th annual meeting of the European Light Microscopy Initiative (ELMI), Oslo, May 20-23, http://www.mn.uio.no/ibv/forskning/aktuelt/arrangementer/konferanser/2014/elmi2014/

PRESENTATIONS TO A TARGETED AUDIENCE AND THE PUBLICChristophersen A. «HLA tetramer to under-stand and diagnose celiac disease. Lecture at the 200-year anniversary seminar of the Faculty of Medicine, September 10, Univer-sity of Oslo, Norway

Lundin KE: «Cøliaki og glutensensitivitet uten cøliaki». Foredrag på årsmøtet for Buskerud NCF, February 18, Hokksund, Norway

Lundin KE: «Non coeliac gluten sensitivity». Lecture at Nordic-baltic AOESC meeting, Scandic KNA Hotel, Oslo, Norway

Lundin KE: «Non-coeliac gluten sensitivity». Foredrag på 40-års jubileum, April 26, Norsk Cøliakiforening, Hotel Bristol, Oslo, Norway

Lundin KE: «Cøliaki og fremtiden». Foredrag på 40-års jubileum, June 26, Norsk Cøliaki-forening, Hotel Bristol, Oslo, Norway

Lundin KE: «Glutensensitivitet uten cøliaki», Foredrag på Med Fak 200 års jubileumssem-inar, May 24, Gamle Festsal, Oslo, Norway

Lundin KE: «Cøliaki». Foredrag på ungdoms leir NCFU, June 23, Elverum, Norway

Lundin KE: «Cøliaki». Foredrag på samling for Norsk Cøliakiforenings Ungdommer Hotell Rica Park Hotell, November 22, Drammen, Norway

Progida C; “How do intracellular compart-ments communicate?” Lab14, October 29, Lillestrøm, Norway

Progida C; “How do intracellular compart-ments communicate?” Lab Norges medlems-møte, November 27, Oslo, Norway

Qiao SW: «Cøliaki – alltid glutenfritt?» Foredrag på Med Fak 200 års jubileums-seminar, May 24, Oslo, Norway

Qiao SW: «Cøliaki og gluten-intoleranse - Er gluten kilden til alt ondt?» Forsknings-dagene, September 21, Oslo, Norway

Rasmus Iversen

Øyvind Steinsbø

57


MEDIA COVERAGELundin KE: Paneldeltager i Dagsnytt 18 om glutensensitivitet: http://radio.nrk.no/serie/dagsnytt-atten/nmag03003714/21-02-2014.

Inger Sandlie, Jan Terje Andersen and col-leagues. "The Research Race to Make Drugs More Efficient". Wall Street Journal May 6. Featuring technology developed by CIR in collaboration with Novozymes.

“Jakter på WOW-effekten”. Geir Åge Løset and Inger Sandlie. http://www.mn.uio.no/forskning/aktuelt/aktuelle-saker/2014/ jakter-pa-wow-effekten.html

«Lanserte HelseOmsorg21 på OUS Riks-hospitalet». The Prime Minister Erna Solberg and Minister of Health and Care Services Bent Høie visited CIR. http://www.oslo-uni-versitetssykehus.no/aktuelt_/nyheter_/Sider/Lanserte-HelseOmsorg21-på-OUS- Rikshospitalet.aspx

“Sykehuset hedrer forskere”. Ludvig Sollid honored with Excellent Researcher Award. http://www.oslo-universitetssykehus.no/aktuelt_/nyheter_/Sider/forskningspris-er-august14.aspx

“Miljonpris til Norges mest citerade for-skare”. Per Brandtzæg. Press release at Lunds Universitet on Fernströmstiftelsens Nordiska Pris: http://www.lu.se/article/mil-jonpris-till-norges-mest-citerade-forskare, and story in Dagens medisin: http://www.dagensmedisin.no/nyheter/per-brandtzag-hedres-med-millionpris/

“UiOs mest oppfinnsomme forsker», Inger Sandlie. Uniforum. http://www.uniforum.uio.no/nyheter/2014/10/uios-mest-opp-finnsomme-forsker.html

«Synliggjør nanoverdenen». Oddmund Bakke in Finansavisen, Oct 9.

«Nobelpris kjemi», NRK Radio live at Oddmund Bakkes lab, Oct 9. http://radio.nrk.no/serie/ekko-hovedsending/MDSP25020114/09-10-2014

«Cinzia Progida vant Lab Norges forskning-spris» at http://messe.no/no/Lab/Nyheter/Cinzia-Progida-vant-Lab-Norges-forsknings-pris/

«Mie (10) og Filippa (12) mistet mamma – nå har de samlet inn 600.000 kroner til kreftsaken». TV2 and the Norwegian Cancer Society visited Audun Tveita at his home in relation to his research grant from the Norwegian Cancer Society. http://www.tv2.no/2014/10/28/nyheter/innsamling/kreft/armband/6170879

Cinzia Progida

Anders Tveita

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Annual Report

IRCentre for Immune Regulation

2010


Redaktør: Lise Kveberg, UiOFoto: Øystein H. Horgmo, UiO

Design: MillimeterpressTrykk: Rolf Ottesen

MILJØMERKET

241 Trykksak 681

CENTRE FOR IMMUNE REGULATION (CIR)

Visiting addressOslo University Hospital-RikshospitaletSognsvannsveien 20 Building A2/A3N-0027 Oslo

Mailing address Centre for Immune Regulation OUS HF, RikshospitaletP.O.Box 4956 Nydalen N-0424 OSLO Norway

Phone (+47) 23 07 35 00Fax (+47) 23 07 35 10Email [email protected]

www.cir.uio.no

cir annual report 2014

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