1. Antigens & HLA
Dr.Ghada Boghdadi

2. Objectives: * Define antigen and hapten.
* Define immunogenicity & antigenicity.
* Define epitope.
* Describe the chemical nature and different classes of Ag.
* Discuss various determinants of antigenicity.
* Describe the major classes of MHC molecule.
* Explain the role of MHC in immune mechanism (antigen processing, antigen presentation & immune response).
Anantha Narayanan
Ch 15

3. Immunogen: A substance that induces a specific immune response.
Antigen (Ag): A substance that reacts with the products of a specific immune response.
Hapten: A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule.
Epitope or Antigenic Determinant: That portion of an antigen that combines with the products of a specific immune response. Any given antigen may have several epitopes. Each epitope is recognized by a different antibody.
Antibody (Ab): A specific protein which is produced in response to an immunogen and which reacts with an antigen.

4. Epitopes: Antigen Regions that Interact with Antibodies

5. FACTORS INFLUENCING IMMUNOGENICITY
A- Immunogen:
1. Foreignness
2. Size
3. chemical composition
4. Physical form
5. Degradability

6. B- Biological system:
1. Genetic factors.
2. Age.

7. C- Method of administration:
1. Dose.
2. Route.
3. Adjuvants.
Substances which are added to or emulsified with an Ag so as to enhance the Ab production.
They can be Inorganic salts : Aluminium hydrooxide
- Bacterial products: Bordetella pertussis (with Diphtheria, Tetanus toxoids)

8. The chemical nature of immunogens:
1. Proteins.
2. Polysaccrides.
3. Nucleic acids.
4. Lipids.

9. Types of Antigens: T-dependent Ag:
Do not directly stimulate the production of antibody without the help of T cells.
- Proteins.
- Immunogenic over a wide dose range and do not cause tolerance.
- Produce immunological memory
- Requires processing by APCs.

10.    T-independent Ag:
Can directly stimulate the B cells to produce antibody without the requirement for T cell help.
Polysaccharides.
- Immune response is dose dependent.
Too little – non immunogenic
Too much – tolerance
Do not produce immunological memory.
- Do not require processing by APCs.
                                                                         

12. Antigen processing and presentation
Exogenous Ag Endogenous Ag

13. Superantigens Not processed.
Interact with the MHC class II molecule outside of the peptide - binding groove.
Bind only to the Vβ segment of TCR.

14. Antigenic specificity:
Species Specificity.
Isospecificity. (Human blood group)
Autospecificity.
Heterogenetic (heterophile) Specificity.

15. Major histocompatibility complex (MHC)
The MHC is a large complex region of highly polymorphic genes located on the short arm of chromosome 6.
Also known as human leukocyte antigens or HLA.
There are 3 classes of MHC molecules: MHC Class I, Class II
and Class III.
. They differ among members of the same species.
. Each person has two haplotypes.

16. MHC class I & II play role in antigen presentation
T cell receptor only recognize antigens combined with major histocompatability (MHC) proteins on the surface of cells.
MHC Class I: Found on all cells.
MHC Class II: Found on phagocytes.
MHC class I & II play role in antigen presentation
For T cell activation, T cell receptor (TCR) must recognize the processed antigens (in peptide fragment forms) which bound to MHC class I or II molecules
(MHC restriction).

18. Table 1. Polymorphism of class I MHC genes
Locus
Number of alleles (allotypes)
HLA-A
218
HLA-B
439
HLA-C 96
HLA-E, HLA-F and HLA-G
Relatively few alleles

19. Table 2. Polymorphism of class II MHC genes Locus
Number of alleles (allotypes)
HLA-DPA HLA-DPB
12 88
HLA-DQA HLA-DQB
17 42
HLA-DRA HLA-DRB1 HLA-DRB3 HLA-DRB4 HLA-DRB5
HLA-DM and HLA-DO
Relatively few alleles