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
SymbolHLA
InterProIPR001039
Membranome63

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, which is to bind an antigen derived from self-proteins, or from pathogens, and bring 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]

  1. ^ Hull P (August 1970). "Notes on Dr Snell's observations concerning the H-2 locus polymorphism". Heredity. 25 (3): 461–5. doi:10.1038/hdy.1970.47. PMID 5275401.
  2. ^ Janeway Jr CA, Travers P, Walport M, et al. (2001). "The Major Histocompatibility Complex and Its Functions". Immunobiology: The Immune System in Health and Disease (5th ed.). New York: Garland Science.
  3. ^ Kimball JW (11 February 2011). "Histocompatibility Molecules". Kimball's Biology Pages. Archived from the original on 4 February 2016.
  4. ^ Janeway Jr CA, Travers P, Walport M, et al. (2001). "The major histocompatibility complex and its functions". Immunobiology: The Immune System in Health and Disease (5th ed.). New York: Garland Science.
  5. ^ Yamazaki K, Boyse EA, Miké V, Thaler HT, Mathieson BJ, Abbott J, et al. (November 1976). "Control of mating preferences in mice by genes in the major histocompatibility complex". The Journal of Experimental Medicine. 144 (5): 1324–35. doi:10.1084/jem.144.5.1324. PMC 2190468. PMID 1032893.
  6. ^ Vigneron N, Stroobant V, Chapiro J, Ooms A, Degiovanni G, Morel S, et al. (April 2004). "An antigenic peptide produced by peptide splicing in the proteasome". Science. 304 (5670): 587–90. Bibcode:2004Sci...304..587V. doi:10.1126/science.1095522. PMID 15001714. S2CID 33796351.