DEPARTMENT OF IMMUNOBIOLOGY

Antigens (Ag)Antigens (Ag)

Xiaowu Hong

xiaowuhong@fudna.edu.cn021-54237093

Department of ImmunologyShanghai Medical College of Fudan University

I Definition and characteristics of antigenI Definition and characteristics of antigen

II Properties of Ag: Foreignness and specificity II Properties of Ag: Foreignness and specificity

III Factors that influence immunogenicity III Factors that influence immunogenicity

IV Classification of antigenIV Classification of antigen

V Nonspecific stimuli for immune responseV Nonspecific stimuli for immune response

antigen

Antigen (Ag)

Chapter 1 Definition of antigenChapter 1 Definition of antigen

Substances that combine combine specificallyspecifically

with a B or T cell’s antigen-binding rece

ptors can then induceinduce an immune respo

nse are called antigens.

Antigen (Ag)

Antigen binding causes cytotoxic T cells

Memory T cell

Activated cytotoxic T cell

Antigen binding triggers release of antibodies

Memory B cell

Activated B cell

Antibodies

Chapter 2 Characteristics of antigen

（ 1 ） immunogenicit

y

（ 2 ） antigenicity

The antigen molecule generally pose The antigen molecule generally pose two natures, that is two natures, that is

(1) Immunogenicity

Immunogenicity is t

he ability to induce a humoral and / or cell mediated immune response, including induce production of antibody and effector lymphocytes.

Activated B cell

antibody

Activated CTL

(2) antigenicity

Antigenicity is the ability to combincombine specificallye specifically with the final products of the above responses (i.e., antibody and /or cell-surface receptors).

antigenicity

immuogenicity

T

TT

Ag

1 SpecificitySpecificity of antigen The characteristic that antigen only binds the antibody and sensitized lymphocyte specifically, is called specificity of antigen （ Specificity ）

Antigenic determinants or epitopes are the i

mmunologically active regions of an immuno

gen that bind to antigen-specific membrane r

eceptors on lymphocytes (TCR/BCR) or to se

creted antibodies.

(1) Antigenic determinants or epitopes

Epitope or An

tigenic Deter

minant

antigen

antigen antigen

1 Conformational epitope

Nonsequential polypeptides or polysaccharide on the sursur

faceface of the molecules,

Native conformationNative conformation,

2 liner epitopeA sequential amino acid fragment,

Linear determinantLinear determinant,

InsideInside of the antigen molecule

Structure of epitopes

Conformational and Linear Epitope

T cell Epitope and B cell EpitopeIn immune response, the epitopes that TCR and BCR recognize is different, and are called T cell epitope and B cell epitope, separately.

（ 1 ） human pancreatic glucagon was inoculated into the mouse

12 3 4 5

67

89

1011

1213

14 1516

17

18NH3

1920

2122

2324

2526

2728

29 COOH

（ 2 ） Production of specific antibody and T effector cell.

antibody ： aim directly at 1~17 amino acids in the N terminal

T effector cell ：aim directly at 18~29 amino acids in the C terminal

No epitope was found to be recognized by T cell and B cell simultaneously.

*natural,

*on the surface of the molecule

* conformational or sequential determinant

* tertiary structure of the molecule

COOH

12 3 4 5

67

89

1011

1213

14 1516

17

18

NH3

1920

2122

2324

2526

2728

29

* Antigenic peptide presented by APC* linear determinant

T cell Epitope and B cell Epitope

T cell Epitope

T cell EpitopeB cell Epitope

Digested

**on surface of molecule antigen

antibodyCDR3

epitope

B cell epitope

is recognized by BCR and antibody

** conformational determinants

(i) B cell epitope

(ii) T cell epitope The peptide that is presented by MHC molecule a

nd recognized by TCR is called T cell epitope .

TCR

MHC

HIV peptide

TCR recognize MHC/antigenic peptide

TCR

Antigenic peptide

MHC-II

T cell

APC

Ep1 Ep2 Ep3

T Cell epitope

Antigenic peptides recognized by T cell form

trimolecular complexes with a TCR and an MHC molecule

Depend on the amino acid sequence of the peptide

Relevant to the expression of MHC molecule of the host

(2) Common antigen and cross-reaction Each B cell determinant induces production of a

specific antibody. Thereby a complicated antigen can

induce production of multiply antibodies.

complicated antigen

A same or similar antigenic determinant

that exists between the two different antigens

is called common antigen .

The reaction that antibody reacts with same or

similar antigenic determinant between the

different antigens is called cross-reaction.

Cowpox vaccineVA

CC

INE Smallpox virus

Bm cell

Immunological memory

ABcowpoxDE

Anti-Cowpox antibody

cowpox Bm cell

Anti- Cowpox antibody against Smallpox

Smallpox Bm cellcowpox Bm cell

days

First response to antigen Cowpox

Antigen Cowpox immunity

Antigen SmallpoxAntigen B immunity

Ant

ibod

y co

ncen

trat

ion First response

to antigen B

Secondary response to antigen Smallpox

Foreignness is the centre of immunogen .

The greater of the phylogenitic distance between two species, the greater the structural disparity between them.

**Various pathogens ,animal protein

**homologuous

**Self-molecule that has not been exposed to immature

lymphocytes during lymphocyte development may be later

recognized as nonself, or foreign,by the immune system.

2 Foreignness

Chapter 3 Factors influencing

immunogenicity

1 Physicochemical nature of antigens

(1) chemical nature glycoprotein, lipoprotein 、 polysaccharide 、 LPS

DNA ， chromosome 、 histone in the activated lymphocyte

Auto-antibody for self-DNA, histone

Antinuclear antibody (ANA)

Autoimmune diseases

(2) molecule size

>10kD

>100kD

<10kD

immunogens

Strong immunogens

Poor immunogens

The higher is the molecule weight

The more are antigenic determinants

The more complex is the antigenic structure

Not be degradated easilier

Stimulating immune cell continuously

High immune response

(3) complicated chemical structure

Glutin MW>100kD ）

Straight chain amino acid Add Aromatic amino acid （ 2% tyrosine ）

（ poor immunogenicity ） （ better immunogenicity ）

(4) conformation and accessibility of the molecule

+++ ± +++

Tyrosine poly-alanine Glutan poly-lysine

immunogenicity

(1) Genetic characteristics of the host

Genetic control of immune responsiven

ess, largely confined to genes within the MH

C.

(2) Age, sex, and state of healthInfection, use of immune inhibitor

2 Effect of host

Chapter 4 Classification of antigens1. Depend on whether need the Th for producing the antibody

** thymus dependent antigen, TD-Ag **thymus independent antigen, TI-Ag

TI and TD antigen

1

2

CD40/CD40L

B cell B cell Th cell

TI- antigen TD antigen

CD4

1 2

(1) Thymus dependent antigen, TD-AgT-dependent Antigens - do not directly stimulate the production of antibody without the help of T cells.

Proteins . Structurally characterized by a few copies of many different antigenic determinants

(2) Thymus independent antigen, TI-AgT-independent Antigens - directly stimulate the B cells to produce antibody without the requirement for T cell help Polysaccharides

Characterized by the same antigenic determinant repeated many times

2 Depend on the relationship with host

(1) Xenogenic Ag ： The antigen from diffe

rent species is called xenogenic antigen.Microorganism Animal immune serum for therapy ： horse serum (antitoxin)

Horse serum antitoxins posses dual natures ：

(i). Specific antibody ---- neutralization of toxin(ii). Xenogenic antigen---stimulate production of antibody against horse serum

toxoidtoxin

Horse serum

antitoxin

hypersensitivity

antibody

antigen

(2) Allogenic Ag ：The antigens from different individuals of the

same species are called allogenic antigen.

Human allogenic Ag ： blood type （ RBC ） antigen Histocompatibility (transplantation) antigens

Blood type ： ABO and Rh

A B O AB

antigen

antibody

A B － A,B

Anti-B anti-A anti-A,anti-B －

Blood type

RBC

+

RBC

complement

RBC

RBC

Type A

A antigen

Type B

Anti-A antibody

Anti-A antibody

transfusion reactiontransfusion reaction

RBC

Autoimmune hemolytic anemia

drug

RBC

Auto-antibody

RBCAg-Ab complex

Activate complement

Membrane of RBC

C9C8

C5b

6 7

(3) AutoantigenInfection, wound and medicine use make the

covercover antigen release or auto-antigen changed or modified, which induce response for auto-antigen.

(4) Hetorophilic antigen, or Forssam antigen

Hemolytic streptococcus B C antigen M antigen

Streptococcus infection

Acute Glomerulonephritis

Glycoprotein of Cardiac valve heart muscle

Rheumatic fever

Streptococcus A

Glomerular basement membra

ne

The hetorophilic antigens are common antigen, which are irrelevant to s

pecies and exist in human, animal, plant and microorganism.

Ⅵ Superantigen, SAg

1 conception:Exceed low dose(1 ～ 10ng/ml) of superantigen is needed to a

ctive 2 ％～ 20 ％ of T cell clones to initiate very strong immune response.

2 category:Exogenous superantigen eg.Staphylococcus aureus enterotoxin A-

E

Endogenous superantigen eg. mouse mammary tumor virus protei

n

3 difference with common antigen ：1 ） low dose, but strong response2 ） not constraint by MHC3 ） recognition is not specific ， and procession and presentation is not required4 ） induce a lot of cytokines releasing, resulting in severe pathologic disease

Ⅶ MitogensSubstances which can active a cluster of lymphocytes including a lot of clones.

Such as ConA, PHA,PWM, LPS and so on.

Nonspecific stimuli for immune responseNonspecific stimuli for immune response

Ⅷ adjuvant1 conceptionAdjuvants (from Latin adjuvare, to help) are substances that, when mixed with an antigen and injected with it, enhance the immunogenicity of that antigen.

2 category

Biological agents: BCG

Inorganic compound:Al(OH)3

Synthesis: cytidine monophosphate(CMP ）， liposome

immunostimulating complex （ ISCOM ）CpG et al which is neotype of adjuvant

Freund‘s complete adjuvant (CFA) and Freund’s non-complete adjuvant (IFA) are co

mmonly used

3 mechanism of actionn Prolong antigen persistencen Enhance co-stimulatory signalsn Induce granuloma formationn Stimulate lymphocyte proliferation nonspecifically

1.Master the concept , characteristic of the antigen, and the factors influencing immunogenicity ( chemical nature, molecule size, foreignness, and genetic characteristics of the host ).2. Master antigenic determinant, common antigen.3.Understand antigen category.4.know superantigen5.Understand the important antigen in medicine.

School of Medicine

Fudan University