Antigens & HLA

Dr.Ghada Boghdadi

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 NarayananCh 15

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.

Epitopes: Antigen Regions that Interact with Antibodies

FACTORS INFLUENCING IMMUNOGENICITY

A- Immunogen:

1. Foreignness

2. Size

3. chemical composition

4. Physical form

5. Degradability

B- Biological system:

1. Genetic factors.

2. Age.

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)

The chemical nature of immunogens:

1. Proteins.

2. Polysaccrides.

3. Nucleic acids.

4. Lipids.

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.

   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.                                                                          

Antigen processing and presentation

Exogenous Ag Endogenous Ag

Superantigens

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

Antigenic specificity:

Species Specificity.

Isospecificity. (Human blood group)

Autospecificity.

Heterogenetic (heterophile) Specificity.

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.

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).

Table 1. Polymorphism of class I MHC genes

LocusNumber of alleles

(allotypes)

HLA-A 218

HLA-B 439

HLA-C 96

HLA-E, HLA-F and HLA-G Relatively few alleles

Table 2. Polymorphism of class II MHC genes

LocusNumber of alleles

(allotypes)

HLA-DPAHLA-DPB

1288

HLA-DQAHLA-DQB

1742

HLA-DRAHLA-DRB1HLA-DRB3HLA-DRB4HLA-DRB5

226930712

HLA-DM and HLA-DO Relatively few alleles