DEPARTMENT OF IMMUNOBIOLOGY
Antigens (Ag)
Xiaowu Hong
xiaowuhong@fudna.edu.cn
021-54237093
Department of Immunology
Shanghai Medical College of Fudan University
antigen
I Definition and characteristics of antigen
II Properties of Ag: Foreignness and specificity
III Factors that influence immunogenicity
IV Classification of antigen
V Nonspecific stimuli for immune response
Chapter 1 Definition of antigen
Antigen (Ag)
Substances that combine specifically
with a B or T cell’s antigen-binding
receptors can then induce an immune
response are called
antigens.
Antigen (Ag)
Antigen binding
triggers release
of antibodies
Antigen binding
causes cytotoxic
T cells
Activated
B cell
Memory
T cell
Activated
cytotoxic T cell
Antibodies
Memory
B cell
Chapter 2 Characteristics of antigen
The antigen molecule generally pose
two natures, that is
（1）immunogenicity
（2）antigenicity
(1) Immunogenicity
Immunogenicity is
the ability to
induce a humoral
and / or cell
mediated immune
response, including
induce production
of antibody and
effector
lymphocytes.
Activated B cell
Activated CTL
antibody
(2) antigenicity
Antigenicity is the
ability to
combine
specifically with
the final products
of the above
responses (i.e.,
antibody and /or
cell-surface
receptors).
antigenicity
T
T
T
Ag
immuogenicity
1 Specificity
Specificity of antigen
The characteristic that antigen only binds the
antibody and sensitized lymphocyte specifically,
is called specificity of antigen（ Specificity ）
(1) Antigenic determinants or epitopes
Antigenic determinants or epitopes are the
immunologically active regions of an
immunogen that bind to antigen-specific
membrane receptors on lymphocytes
(TCR/BCR) or to secreted antibodies.
antigen
Epitope or
Antigenic
Determinant
antigen
antigen
Structure of epitopes
1 Conformational epitope
Nonsequential polypeptides or polysaccharide on the
surface of the molecules,
Native conformation,
2 liner epitope
A sequential amino acid fragment,
Linear determinant,
Inside of the antigen molecule
Conformational and Linear Epitope
T cell Epitope and B cell Epitope
In 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
NH3
1
2 3 4 5
10
11
6
7
8
9
12
17
13
16
14 15
18
19
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23
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29
COOH
（2）Production of specific antibody and T effector cell.
No epitope was found to be recognized
by T cell and B cell simultaneously.
NH3
1
2 3 4 5
10
11
T effector cell：
aim directly at
18~29 amino
acids in the C
terminal
6
7
8
9
12
17
13
16
14 15
18
19
20
21
22
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24
25
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COOH
antibody：aim
directly at 1~17
amino acids in
the N terminal
* Antigenic
peptide
presented
by APC
* linear
determinant
*natural,
*on the surface of the molecule
* conformational or sequential determinant
* tertiary structure of the molecule
T cell Epitope and B cell Epitope
T cell Epitope
Digested
B cell Epitope
T cell Epitope
(i) B cell epitope
B cell epitope
epitope
is recognized by BCR
and antibody
**on surface of molecule
antigen
** conformational determinants
antibody
CDR3
(ii) T cell epitope
peptide that is presented by MHC molecule
and recognized by TCR is called T cell epitope .
The
MHC
HIV peptide
TCR
TCR recognize MHC/antigenic peptide
T cell
TCR
Antigenic peptide
MHC-II
APC
T Cell epitope
Ep1
Ep2
Ep3
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 vaccine
Smallpox virus
Bm cell
Immunological memory
Anti-Cowpox antibody
Anti- Cowpox antibody
against Smallpox
A
B
cowpox
D
E
cowpox Bm cell
Smallpox Bm cell
cowpox Bm cell
Antibody concentration
Secondary response
to antigen Smallpox
First response to
antigen Cowpox
Antigen Cowpox
immunity
First response
to antigen B
Antigen Smallpox
Antigen B
days
immunity
2 Foreignness
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.
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
The higher is the
molecule weight
(2) molecule size
>10kD
immunogens
>100kD
Strong immunogens
<10kD
Poor immunogens
The more are antigenic
determinants
The more complex is
the antigenic structure
Not be degradated easilier
High
immune
response
Stimulating immune cell continuously
(3) complicated chemical structure
Glutin MW>100kD ）
Straight chain amino acid
（poor immunogenicity）
Add Aromatic amino acid（2% tyrosine）
（better immunogenicity）
(4) conformation and accessibility of the molecule
immunogenicity
±
+++
Tyrosine
poly-alanine
Glutan
+++
poly-lysine
2 Effect of host
(1) Genetic characteristics of the host
Genetic control of immune
responsiveness, largely confined to genes
within the MHC.
(2) Age, sex, and state of health
Infection, use
of immune
inhibitor
Chapter 4 Classification of antigens
1. Depend on whether need the Th for
producing the antibody
** thymus dependent antigen, TD-Ag
**thymus independent antigen, TI-Ag
TI and TD antigen
TI- antigen
TD antigen
CD4
1
2
1
2
CD40/CD40L
B cell
B cell
Th cell
(1) Thymus dependent antigen, TD-Ag
T-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-Ag
T-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 different
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
toxin
toxoid
Horse serum
antibody
hypersensitivity
antigen
antitoxin
(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
Blood type
A
B
O
AB
antigen
A
B
－
A,B
Anti-B
anti-A
antibody
anti-A,anti-B
－
A antigen
Anti-A antibody
RBC
Type A
Type B
complement
RBC
RBC
transfusion reaction
Anti-A antibody
+
RBC
(3) Autoantigen
Infection, wound and medicine use make the
cover antigen release or auto-antigen changed or
modified, which induce response for auto-antigen.
drug
RBC
RBC
RBC
Auto-antibody
Activate complement
Autoimmune hemolytic anemia
6 7
C C
5b 8
C9
Membrane of RBC
(4) Hetorophilic antigen, or Forssam antigen
The hetorophilic antigens are common antigen, which are irrelevant to
species and exist in human, animal, plant and microorganism.
Hemolytic streptococcus B C antigen
M antigen
Glycoprotein of Cardiac valve
heart muscle
Streptococcus A
Rheumatic fever
Streptococcus infection
Acute
Glomerulonephritis
Glomerular
basement
membrane
Ⅵ Superantigen, SAg
1 conception:Exceed low dose(1～10ng/ml) of superantigen is needed to
active 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 protein
3 difference with common antigen：
1）low dose, but strong response
2）not constraint by MHC
3）recognition is not specific，and procession and presentation is not
required
4）induce a lot of cytokines releasing, resulting in severe pathologic
disease
Nonspecific stimuli for immune response
Ⅶ Mitogens
Substances which can active a cluster of
lymphocytes including a lot of clones.
Such as ConA, PHA,PWM, LPS and so on.
Ⅷ adjuvant
1 conception
Adjuvants (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
commonly used
3 mechanism of action
n Prolong antigen persistence
n Enhance co-stimulatory signals
n Induce granuloma formation
n 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 superantigen
5.Understand the important antigen in
medicine.
Fudan University
School of Medicine