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 Narayanan Ch 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.

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).

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

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 2 269 30 7 12 HLA-DM and HLA-DO Relatively few alleles