abbr.: MHC; a complex of genetic loci occurring in higher vertebrates that encodes a family of cellular antigens, known in mice as
histocompatibility-2 antigens (
abbr.: H-2 antigens; see
histocompatibility antigen) and in humans as human leukocyte-associated antigens (
abbr.: HLA antigens; see
HLA histocompatibility system). The MHC antigens are cell-surface glycoproteins and may be divided into two classes, designated I and II. In transplantation reactions, cytotoxic T lymphocytes respond mainly against foreign MHC glycoproteins of class I together with antigen, while the response against class II and antigen is mainly by helper T lymphocytes.
Class I MHC antigens (
or transplantation antigens) are on the surface of most nucleated somatic cells and enable the immune system to distinguish self from foreign cells. They are encoded by three separate loci (H-2K, H-2D, and H-2L in mice; HLA-A, HLA-B, and HLA-C in humans). The antigenic activity resides in a transmembrane polypeptide chain, the α subunit, of ≈45 kDa (roughly 345 amino acids), which has a short hydrophilic C-terminal segment inside the cell and a large glycosylated N-terminal segment. The latter is folded into three separate domains (two of which contain an intrachain disulfide bond) and exposed to the cell exterior, where it is noncovalently linked with the β subunit (of 11.5 kDa and also called β
2 microglobulin), which is homologous with a single Ig-like domain (see
immunoglobulin fold). In humans, these proteins are also referred to as
HLA class I.
Class II MHC antigens are found on the surface of most B lymphocytes, some T lymphocytes, and some macrophages and macrophage-like cells. They are encoded by murine I-region (
abbr.: Ir) genes and human HLA-D genes, and contain a ≈33 kDa α chain and a 28 kDa β chain; the C-terminal regions of both subunits have transmembrane and intracellular domains. Celiac disease is due to an allelic variant in one class-II gene.