Antigens (Ag)

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Antigens (Ag) Xiaowu Hong xiaowuhong_at_fudna.edu
.cn 021-54237093 Department of Immunology Shanghai
Medical College of Fudan University
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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
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Chapter 1 Definition of antigen
Antigen (Ag)
Substances that combine specifically with a B or
T cells antigen-binding receptors can then
induce an immune response are called antigens.
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Antigen (Ag)
Antigen binding triggers release of antibodies
Antigen binding causes cytotoxic T cells
Activated B cell
Memory T cell
Activated cytotoxic T cell
Memory B cell
Antibodies
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Chapter 2 Characteristics of antigen
The antigen molecule generally pose two natures,
that is

• (1)immunogenicity
• (2)antigenicity

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(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
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(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).
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antigenicity
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Antigen and Adaptive immunity
B cells antigen
Effector B cells memory B cells
(Plasma cell)
T cells antigen
Effector T cells memory T cells
(CTLs, Th)
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1 Specificity
Specificity of antigen The characteristic
that antigen only binds the antibody and
sensitized lymphocyte specifically, is called
specificity of antigen( Specificity )
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(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.
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Epitope or Antigenic Determinant
antigen
antigen
antigen
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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
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Conformational and Linear Epitope
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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
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COOH
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(2)Production of specific antibody and T effector
cell.
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No epitope was found to be recognized by T cell
and B cell simultaneously.
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COOH
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T cell Epitope and B cell Epitope
T cell Epitope
Digested
B cell Epitope
T cell Epitope
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(i) B cell epitope
B cell epitope
is recognized by BCR and antibody
epitope
antibodyCDR3
on surface of molecule
antigen
conformational determinants
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Determinants recognized by B cells
1. Composition - Antigenic determinants
recognized by B cells and the antibodies secreted
by B cells are created by the primary sequence of
residues in the polymer (linear or sequence
determinants) and/or by the secondary, tertiary
or quaternary structure of the molecule
(conformational determinants). 2. Size - In
general antigenic determinants are small and are
limited to approximately 4-8 residues. (amino
acids and or sugars). The combining site of an
antibody will accommodate
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(ii) T cell epitope
The peptide that is presented by MHC
molecule and recognized by TCR is called T cell
epitope .
MHC
HIV peptide
TCR
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TCR recognize MHC/antigenic peptide
T cell
TCR
Antigenic peptide
MHC-II
APC
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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
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Determinants recognized by T cells

1. Composition - Antigenic determinants recognized
   by T cells are created by the primary sequence of
   amino acids in proteins.
2. T cells do not recognize polysaccharide or
   nucleic acid antigens.
3. The determinants need not be located on the
   exposed surface of the antigen since recognition
   of the determinant by T cells requires that the
   antigen be proteolytically degraded into smaller
   peptides.
4. Free peptides are not recognized by T cells,
   rather the peptides associate with molecules
   coded for by the major histocompatibility complex
   (MHC) and it is the complex of MHC molecules
   peptide that is recognized by T cells.

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Comparison of epitope of T and B cell
T cell epitope B cell epitope
Receptor TCR
BCR
MHC molecule required to display none
required processed
antigen
character liner peptides
natural polypeptide,LPS,

polysaccharide,
organic compound
8 12 amino acids (CD8) ,12 17 amino acids
(CD4)
515 amino acids, 57 monosaccharide or 57
nucleotide
size
Epitope type liner
conformational, liner
side any
on the surface
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(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
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A same or similar antigenic determinant
that exists between the two different antigens is
called common antigen .
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The reaction that antibody reacts with same
or similar antigenic determinant between the
different antigens is called cross-reaction.
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(No Transcript)
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Immunological memory
Anti-Cowpox antibody
Anti- Cowpox antibody against Smallpox
A B cowpox D E
cowpox Bm cell
Smallpox Bm cell
cowpox Bm cell
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Secondary response to antigen Smallpox
Antibody concentration
First response to antigen Cowpox
First response to antigen B
days
Antigen Cowpox immunity
Antigen Smallpox Antigen B
immunity
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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.
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1.3. Hapten and Carrier
1 Hapten some small molecules, called
haptens, are antigenic but incapable,by
themselves, of inducing a spedific immune
response. In other words, they lack immunogenicity
2 carrier Chemical coupling of hapten to a large
protein yields an immunoginic hapten-carrier
conjugate. The substance that can make the
hapten be immunogenic ( is capable of inducing
immune response) are called carrier.
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Hapten
carrier

small molecules
A substance that is non-immunogenic but which can
react with the products of a specific immune
response.
immune response
Haptens have the property of antigenicity but not
immunogenicity.
haptencarriercomplete antigen
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Chapter 3 Factors influencing immunogenicity
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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
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The higher is the molecule weight
(2) molecule size
gt10kD
immunogens
The more are antigenic determinants The more
complex is the antigenic structure
gt100kD
Strong immunogens
lt10kD
Poor immunogens
Not be degradated easilier
High immune response
Stimulating immune cell continuously
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(3) complicated chemical structure
Glutin MWgt100kD )
Straight chain amino acid
Add Aromatic amino acid(2 tyrosine)
(poor immunogenicity)
(better immunogenicity)
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(4) conformation and accessibility of the molecule
immunogenicity
Tyrosine poly-alanine Glutan
poly-lysine
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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
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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
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TI and TD antigen
TI- antigen
TD antigen
CD4
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2
CD40/CD40L
B cell
B cell
Th cell
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(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
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(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
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2 Depend on the relationship with host
(1) Xenogenic AgThe 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
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hypersensitivity
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(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
Blood type
antigen
A B -
A,B
antibody
Anti-B anti-A anti-A,anti-B
-
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Anti-A antibody
A antigen
Anti-A antibody
Type A
Type B
complement

RBC
transfusion reaction
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(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
Ag-Ab complex
RBC
RBC
RBC
Auto-antibody
Activate complement
Autoimmune hemolytic anemia
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C8
C 5b
C9

Membrane of RBC
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(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
Streptococcus infection
Rheumatic fever
Glomerular basement membrane
Acute Glomerulonephritis
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? Superantigen, SAg 1 conceptionExceed low
dose(110ng/ml) of superantigen is needed to
active 220 of T cell clones to initiate very
strong immune response. 2 categoryExogenous
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
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Nonspecific stimuli for immune response
? Mitogens Substances which can active a cluster
of lymphocytes including a lot of clones. Such
as ConA, PHA,PWM, LPS and so on.
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? 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
compoundAl(OH)3 Synthesis cytidine
monophosphate(CMP),liposome immunostimulating
complex(ISCOM) CpG et al which is neotype of
adjuvant Freunds complete adjuvant (CFA) and
Freunds 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
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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.
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