Major Histocompatibility Complex, MHC

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Major histocompatibility complex (MHC) is the group of genes located at the long arm of chromosome 6 in humans and chromosomes 17 in mice. They are also called Human Leucocyte Antigen (HLA) complex in humans and H-2 complex in mice. They play important roles in intercellular recognition and in differentiation between self and nonself.

MHC genes encode molecules (proteins) expressed on the surface of cells. Three different types of MHC genes encode the different molecules as:

    1. Class I MHC
    2. Class II MHC
    3. Class III MHC

Class I MHC

Class I MHC genes are at the locus of A, B and C at the chromosome 6 in humans. Genes encode glycoproteins expressed on most nucleated cells.

Class II MHC

Class II MHC genes are at the loci DP, DQ and DR at chromosome 6 in humans.These genes encode glycoproteins expressed on mainly on antigen presenting cells (APCs) such as macrophages, B cells and dendritic cells. The peptide processed by APCs will be expressed and presented on class II MHC molecules.

Class II MHC

Genes are at loci C4, C2 and BF at chromosome 6 in humans. They encode other immune proteins such as components in complement system, inflammatory cytokines, including tumor necrosis factor (TNF) and heat-shock proteins.

Class I and Class II MHC

Class I and Class II have the similarity where both process antigens.

Structure of Class I and Class II MHC

Both are membrane bound glycoproteins. Class I MHC have 45-kilodalton (kDa) α chain and 12-kDa β2-microglobulin molecule. α and β are associated non covalently. The α  chain is anchored inside the plasma membrane by its hydrophobic transmembrane segment and hydrophilic cytoplasmic tail. α chain make up α1, α2 and α3 as external domains. Each contains roughly 90 amino acids. Transmembrane is make up by about 25 hydrophobic amino acids followed by a short stretch of charged (hydrophilic) amino acids. β2-microglobulin does not have transmembrane segment. α1 and α2 form peptide binding cleft where the processed peptide is bound and expressed.

Class II MHC have 33-kDa α chain and a 28-kDa  β chain. These two chains are associated non covalently. Class II molecules have external domains and transmembranes as Class I molecules. α1 and β1 domains make up the peptide binding cleft for processed peptide/antigen. α and β chains form the transmembrane segment each.

MHC Class I and II

MHC Class I and II
(Image credit: Kuby Immunology)