ANTIGENS

Lecture 2

ANTIGENS,
ANTIGEN RECOGNITION AND
PRESENTATION

1.
2.
3.
4.
5.

Husam Samara

6.

The structure of antigens

Antigen processing and presentation
Peptide-MHC molecule: structure and
assembly
Antigen recognition by B and T cells
Superantigens
Stress proteins (heat shock proteins)

20010/2011

Antigens

The structure of antigens

Proteins, peptide chains,

carbohydrates, glycoproteins,
synthetic molecule.

Structure of the molecule:

Definition:
A molecule, or part of a molecule that can be specifically
recognized by the immune system
Antigens are recognized by elements of adaptive immunity:
Receptors on T and B cells
Immunoglobulins

Aminoacid

sequence,
conformation,
Type of aa., charge,
Modifications and additional residues.
3D

Immunogenicity:
The ability of a molecule to elicit specific immune
response

Epitopes the antigenic

determinants
Epitope: the site of antigen recognized by
receptor
One antigen may contain more than one
epitope, or repeated epitopes.
Diversity of epitopes on a certain antigen
is responsible for the polyclonal immune
response.
Different receptors recognize different
forms of antigens.

Haptens

Small particles, not immunogenic by themselves.

Need a carrier protein to be recognized.
Antibodies may be produced against the hapten
itself or the hapten-carrier conjugate
(neoantigen).
Significance of haptens:
Immunity

to drugs
autoimmune diseases
Contact hypersensitivity
Drug-induced

TYPES OF ANTIGENS INVOLVED IN

PATHOGENESIS OF DISEASES
9

Microbial antigens (bacterial, viral, fungal, parasitic)

Blood group antigens

Transplantation alloantigens (MHC)

Allergens

Autoantigens (organ and/or tissue specific)

Tumor antigens (tumor specific and t. associated)

Superantigens: eg.SEB-staphylococcal enterotoxin B

Heat shock proteins

Antigen Presentation
Uptake
Processing
Introduction
of antigens to effector cells
Stimulation

Antigen Presenting Cells (APCs)

Modes of antigen presentation

Molecules involved in antigen presentation

TCR BCR
MHC-II MHC-I

Major histocompatibility complex

(MHC)

Known in human as Human Leukocyte Antigen (HLA)

Transmembrane complex of several protein chains and
domains
Encoded by genes on the chromosome 6.
Responsible for antigen presentation by Antigen
Presenting Cells (APCs)
Three classes:

Via MHC class I

Via MHC class II

Cross presentation

Recognition of antigens by B-cell receptors.

In terms of antigen source:

Presentation of intrinsic antigens

Presentation of extrinsic antigens

MHC genes

Polymorphic. CoCo-dominant. 100

100s of alleles for each HLA.
Transplantation

MHC class I HLA -A, -B, -C, -E

MHC class II HLA-DP, -DQ, -DR
MHC class III complement C2, C4, factor B, TNF, HSPs

Pathways of antigen processing

MHC class I

Transmembrane
complex which
consists of:

Three

domains
1-3
2-microglobulin
Transmembrane
region
Cytoplasmic tail

PEPTIDE BINDING BY MHC CLASS I

AND CLASS II MOLECULES

Presentation of intracellular antigens

Presentation of extrantracellular antigens

MHC TCR interaction

Good
Good fit
fit

Poor
Poor fit
fit

better
better presentation
presentation
worse
worse presentation
presentation

Cross-presentation

Extracellular antigens
are presented by
MHC class I
Essential role in
antitumor immunity
Role in immunity to
infectious pathogens:
vaccines with viral
antigens elicit cellular
response

3rd

2nd

1st

3rd
2nd

E.g.

Three signals
Immunologic synapse

MHC
RESTRICTION

A T cell recognizes a peptide antigen only when

it is bound to a particular MHC molecule
Role in the T cell recruitment in the thymus

T-cell Receptor (TCR)

A membrane receptor for antigens presented by APCs

Heterodimer which consists of and or and
chains linked to each other by SH-SH bridge
Complementarity determining regions (CDRs):
portions of the and chains fold into a structure that
resembles the antigen-binding portion (Fab) of an
antibody, they are responsible for antigen binding
CD3 complex:
polypeptide invariant chains (, , , and ) associated
with antigen binding domain and capable of transmitting
a signal into the cell upon binding to an antigen

T-cell Receptor (TCR)

Co-receptor molecules CD4 and

CD8 are associated with TCR and
help stabilize the interaction with
MHC, they determine the a

TCR variable region gene diversity

is generated by V(D)J
recombination

read more about the assembly of

gene products of TCR and
immunoglobulins!!

B-cell receptor
Read more about the MHC class II-mediated
antigen presentation!

Is a surface IgM on mature B lymphocytes

Recognizes folded proteins or
glycoproteins (3D structure).
Each cell recognizes one epitope, the
activation of this receptor induces the
internalization of the receptor degradation
and the antigen presentation by MHC-II to
helper T cells

SUPERANTIGENS

Molecules capable of binding MHC and TCR in an

atypical non-specific manner.
Activate T cells independently form their specificity
Provide to massive clone-nondependent activation of
lymphocytes,
Examples:
staphylococcal enterotoxins (SEB) responsible for some
types of acute food poisoning,
toxic shock syndrome toxin-1 (TSST-1) responsible for
tampon sepsis-induced shock
exfoliative dermatitis toxin.