analysis of the sequences, genes and 3d structures of the ... · l-part1 l-part2 v-region 1st-cys...

The international ImMunoGeneTics information system®Coordinator: M.-P. Lefranc, Montpellier, France http://imgt.cines.fr

Analysis of the sequences, genes and3D structures

of the immunoglobulins, T cell receptors and MHC using the IMGT databases, tools and Web

resourceshttp://imgt.cines.fr

Marie-Paule LefrancUniversité Montpellier, CNRS

Institut Universitaire de France


IMGT domain of research: the adaptive immune system

Immunoglobulin

B cellT cell

T cell Receptor MHC

peptide

Trimolecular complex

Vertebrates

Immunoglobulin IgG

IMGT

Immunoglobulin (IG) T cell receptor (TR)

Membrane IgM T cell receptor

Heavy chain

Light chain

Alpha - Beta

Gamma - Delta

Contribution of the2 V-DOMAINs

to the antigen binding siteV-J-REGION

V-J-REGION

V-D-J-REGION

V-DJ-REGION

The adaptive immune system – The biological context

V-DOMAIN

V-DOMAIN

Immunoglobulin IgMhttp://imgt.cines.fr

1 V-DOMAIN4 C-DOMAINs

1 V-DOMAIN

1 C-DOMAINLight chain

Heavy chain mu

Immunoglobulin synthesis

rearrangedDNA

mRNA

genomic DNA(IGH Locus 14q32)

5’ 3'

V D J C

5’ 3'

2 x 1012 different IGper individual

http://imgt.cines.fr

Immunoglobulin (IG) synthesis


2 x 1012

DIFFERENT ANTIBODIES

5 ' 5 '3 ' 3 'x 1000

6300 POTENTIAL RECOMBINATIONS POTENTIAL RECOMBINATIONSN-DIVERSITY

SOMATIC MUTATIONS

ABOUT POSSIBILITIES3.5 x 105ABOUT POSSIBILITIES6.3 x 106

185 +165

15 0FUNCTIONAL IG GENES

5 ' 3 '

V D J C

39 - 4 6 x 2 3 x 6 34 - 37 x 5 Kappa30 - 33 x 4 -5 Lambda

5 ' 3 '

V J CHEAVY CHAIN LIGHT CHAIN

5' 3'

An example of V-GENE

V-INTRONL-PART1 V-REGIONL-PART2

1st-CYS23

2nd-CYS104

DONOR

-SPLICE

ACCEPTOR

-SPLICE

5'UTR 3'UTR

V-HEPTAMER

V-NONAMERV-SPACER

V-RS

tgagagctcc gttcctcacc atggactgga cctggaggat cctcttcttg gtggcagcag 60ccacaggtaa gaggctccct agtcccagtg atgagaaaga gattgagtcc agtccaggga 120gatctcatcc acttctgtgt tctctccaca ggagcccact cccaggtgca gctggtgcag 180tctggggctg aggtgaagaa gcctggggcc tcagtgaagg tctcctgcaa ggcttctgga 240tacaccttca ccggctacta tatgcactgg gtgcgacagg cccctggaca agggcttgag 300tggatgggat ggatcaaccc taacagtggt ggcacaaact atgcacagaa gtttcagggc 360agggtcacca tgaccaggga cacgtccatc agcacagcct acatggagct gagcaggctg 420agatctgacg acacggccgt gtattactgt gcgagagaca cagtgtgaaa acccacatcc 480tgagggtgtc agaaacccaa gggaggaggc ag

>X62106.0|HSVI2|Homo sapiens VI-2 gene for immunoglobulin heavy chain

aa gaggctccct agtcccagtg atgagaaaga gattgagtcc agtccagggagatctcatcc acttctgtgt tctctcca

tgaaa acccacatcctgagggtg

5' 3'5'UTR 3'UTR

An example of D-GENE

D-REGION

5’D-HEPTAMER

5’D-NONAMER5’D-SPACER

>J00256|IGHD7-27*01|Homo sapiens D-GENE

3’D-NONAMER

3’D-HEPTAMER3’D-SPACER

ccagccgcag ggtttttggc tgagctgaga accactgtgc taactgggga cacagtgatt 60ggcagctcta caaaaaccat gctcccccgg g

c tgagctgaga ac attggcagctct

5’D-RS 3’D-RS

5' 3'5'UTR 3'UTR

An example of J-GENE

>J00256|IGHJ1*01|Homo sapiens J-GENE

J-REGION

J-HEPTAMER

J-NONAMERJ-SPACER

DONOR

-SPLICE

J-TRP118

accccgggct gtgggtttct gtgcccctgg ctcagggctg actcaccgtg gctgaatact 60tccagcactg gggccagggc accctggtca ccgtctcctc aggtgagtct gctgtactgg 120ggatagcggg gagccatgtg tactgggcca agcaagggct ttggcttcag 170

gcccctgg ctcagggctg act

Heavy chain WGXG (J-TRP)Light chain FGXG (J-PHE)

J-RS

JUNCTION

gatttgtgcgaaa gtggtgactgctat actcctgg

3’V-REGION D-REGION 5’J-REGION

agcatattgtg acaactggttcg

Immunoglobulin V-D-J generationof sequence diversity

N-REGION

tcctacc

N-REGION

ga

C A P Y R G D T Y D Y S Wtgtgcgcca ggggtgactactattgt gcg cca tac cgg ggt gac act tat gat tac tcc tgg


IMGT Repertoire 8,000 HTML pages HTML

Chromosomal localizationsLocus representations, …

IMGT Bloc-notesInteresting linksThe IMGT Immunoinformatics page

(databases, tools, resources, …)

IMGT EducationTutorials, IMGT Lexique, …

IMGT® Web Resources


Human IGH locus

Chromosome14q32.33

Human IGHV genes at chromosome 14q32.33


Alignmentof alleles

ProteinDisplay

Collier de Perles

The eleven IMGT amino acid classes according to the physico-chemical properties

(Pommié et al. J. Mol Recogn. 17:17-32, 2004)

IMGT databases and tools



IMGT/V-QUEST

Example of IMGT/V-QUEST results

V-GENE J-GENEJUNCTION


IMGT/JunctionAnalysis


View from above the CDRsSide view of the V-DOMAINs

V-J junctionV-D-J junction

V-DOMAINs: VH and V-KAPPA http://imgt.cines.fr

Mouse(Mus musculus) E5.2Fv CDR3-IMGT= Complementarity determining region (105-117)V-J junction (104-118)V-D-J junction (104-118)

V-KAPPAVH V-KAPPAVH

IMGT/3Dstructure-DB and

IMGT/StructuralQuery


Tot

NCo

Pol

HB

NPol

Cov

SS

Number of non covalent atomic

Total number of atomic pair contacts

Number of polar atomic pair contactsNumber of hydrogen bonds

Number of non polar atomic pair contactsNumber of covalent links (other than chain covalent links)Number of disulfide bridges

41V - TRP (W)

chain : 1u8k_B

From IMGT Colliers de Perles or from domain/chain sequence

IMGT Collier de Perleshttp://imgt.cines.fr

analysis of the sequences, genes and 3d structures of the ... · l-part1 l-part2 v-region 1st-cys...

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