Major Histocompatability Complex MHC

Common features of all Class I and II molecules

These are transmembrane glycoproteins molecules for recognition and processing of antigen and stimulation of next stages of immune response

They have grooves, each groove specific to certain peptide antigen (epitope) binding compatible to its size,

Expressed co-dominantly on cell surface

Three regions of each protein

–        Peptide-binding variable region

–        Constant region

–        Transmembrane region

Class I MHC molecules:

1-Present in all nucleated cells

2-Bind to endogenous antigens degraded in the cytosol

e.g., viral proteins, Brucella

3-Present peptide to CD8 T cytotoxic cells

4-Composed of 1 δ peptide chain,

 The chain consists of 5 domains,

         3 extracellular(δ1, δ2, δ3) 1 trans membranous(δ4), 1 intracytoplasmic(δ5)

         Each domain consists of 100 A.A

5- Presence of B2 Microglobulin as support to the chain

6-The groove composed of two domains δ1 & δ2 within the same chain

7-Responsible about T-cell mediated (Toxicity) immunity

Class II MHC molecules:

1-Present in APC only

2-Bind to exogenous antigens degraded in endocytic vesicles

e.g., bacteria, dead virus

3-Present peptide to CD4 T helper cells

4-Composed of 2 (δ and B)peptide chains, each chain consists of 4 domains and linkage

         2 extracellular(δ1 & δ2/B1&B2), 1 trans membranous(δ3&B3), 1 intracytoplasmic(δ4&B4)

5-No B2 Microglobulin

6-The groove composed of two domains δ1 & B1 of 2 different chains

7-Responsible about T helper mediated ( humoral)immunity

General genomic organization of MHC

Chromosome 6 in human encoding genes responsible for production of MHC protein

Three major subregions

–        “Classical” MHC: Class I and II while Class III of less important

–        Transmitted hereditary as a group

–        Up to 6 to 60 loci per class, but typically only 2 to 3 are highly expressed,

 that’s why it’s difficult to be genetically engineered

–        Extensive polymorphism, up to 60 to 100 alleles

–        most individuals are heterozygous and few are identical in a random-breeding population

–        Relative marriage decrease variation in MHC decrease immunity and vice versa

–        Moreover MHC genes responsible about:

1-Phermones: so Rat of similar pheromones never mating

2-Disease susceptibility: some cow breed resistance to Brucella and Mastitis