MHCklasse

MHCklasse refers to the class of genes encoding the major histocompatibility complex (MHC) proteins that present peptide antigens to T lymphocytes in jawed vertebrates. The MHC is a gene-dense region with high polymorphism, located in the MHC locus on chromosome 6 in humans (HLA). The MHC shows co-dominant expression, meaning individuals inherit and express multiple variants from both parents.

MHC class I molecules are composed of a heavy chain (alpha chain) associated with beta-2 microglobulin. Their peptide-binding groove is formed by the alpha1 and alpha2 domains. They present endogenous peptides, typically from intracellular proteins, to CD8+ cytotoxic T cells. Peptides are generated by the proteasome in the cytosol and transported into the endoplasmic reticulum by TAP transporters before loading onto the MHC I molecule.

MHC class II molecules consist of an alpha and a beta chain, with a peptide-binding groove formed by the alpha1 and beta1 domains. They present exogenous peptides to CD4+ helper T cells. Peptide loading occurs in endosomal/lysosomal compartments, aided by the invariant chain, CLIP, and HLA-DM. MHC II is mainly expressed on professional antigen-presenting cells such as dendritic cells, macrophages, and B cells, though expression can be induced on other cell types under inflammatory conditions.

Genetics and evolution: humans possess multiple class I loci (e.g., HLA-A, -B, -C) and class II loci (e.g., HLA-DR, -DQ, -DP). The class III region, between classes I and II, encodes various other immune components like certain complement proteins and cytokines. The extensive polymorphism of MHC genes underpins diverse antigen presentation and influences immune responses.

Clinical relevance: MHC compatibility affects organ and tissue transplantation outcomes; certain MHC alleles correlate with susceptibility to autoimmune diseases and infections; MHC typing informs vaccine design and immunotherapies.