Major histocompatibility complex

Major histocompatibility complex molecule
Major histocompatibility complex protein (class I) in orange and pink, with a presented peptide in red. Membrane in grey. The transmembrane and cytoplasmic domains are shown in cartoon form. (PDB: 1hsa​)
Identifiers
Symbol	HLA
InterPro	IPR001039
Membranome	63

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.

The name of this locus comes from its discovery through the study of transplanted tissue compatibility.^[1] Later studies revealed that tissue rejection due to incompatibility is only a facet of the full function of MHC molecules: binding an antigen derived from self-proteins, or from pathogens, and bringing the antigen presentation to the cell surface for recognition by the appropriate T-cells.^[2] MHC molecules mediate the interactions of leukocytes, also called white blood cells (WBCs), with other leukocytes or with body cells. The MHC determines donor compatibility for organ transplant, as well as one's susceptibility to autoimmune diseases.

In a cell, protein molecules of the host's own phenotype or of other biologic entities are continually synthesized and degraded. Each MHC molecule on the cell surface displays a small peptide (a molecular fraction of a protein) called an epitope.^[3] The presented self-antigens prevent an organism's immune system from targeting its own cells. The presentation of pathogen-derived proteins results in the elimination of the infected cell by the immune system.

Diversity of an individual's self-antigen presentation, mediated by MHC self-antigens, is attained in at least three ways: (1) an organism's MHC repertoire is polygenic (via multiple, interacting genes); (2) MHC expression is codominant (from both sets of inherited alleles); (3) MHC gene variants are highly polymorphic (diversely varying from organism to organism within a species).^[4] Sexual selection has been observed in male mice choosing to mate with females with different MHCs.^[5] Also, at least for MHC I presentation, there has been evidence of antigenic peptide splicing, which can combine peptides from different proteins, vastly increasing antigen diversity.^[6]