Major histocompatibility complex

The major histocompatibility complex (MHC) is a set of genes that code for cell surface proteins essential for the acquired immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility. The main function of MHC molecules is to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells. MHC molecules mediate interactions of leukocytes, also called white blood cells (WBCs), which are immune cells, with other leukocytes or with body cells. The MHC determines compatibility of donors for organ transplant, as well as one's susceptibility to an autoimmune disease via crossreacting immunization. The human MHC is also called the HLA (human leukocyte antigen) complex (often just the HLA). The MHC in mice is called the H-2 complex or H-2. The major histocompatibility complex (MHC) is a set of genes that code for cell surface proteins essential for the acquired immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility. The main function of MHC molecules is to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells. MHC molecules mediate interactions of leukocytes, also called white blood cells (WBCs), which are immune cells, with other leukocytes or with body cells. The MHC determines compatibility of donors for organ transplant, as well as one's susceptibility to an autoimmune disease via crossreacting immunization. The human MHC is also called the HLA (human leukocyte antigen) complex (often just the HLA). The MHC in mice is called the H-2 complex or H-2. 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 molecular fraction of a protein, called an epitope. The presented antigen can be either self or non-self, thus preventing an organism's immune system targeting its own cells. In its entirety, the MHC population is like a meter indicating the balance of proteins within the cell. The MHC gene family is divided into three subgroups: MHC class I, MHC class II, and MHC class III. Class I MHC molecules have β2 microglobulin subunit which can only be recognised by CD8 co-receptors. Class II MHC molecules have β1 and β2 subunits and can be recognised by CD4 co-receptors. In this way MHC molecules chaperone which type of lymphocytes may bind to the given antigen with high affinity, since different lymphocytes express different T-Cell Receptor (TCR) co-receptors. Diversity of antigen presentation, mediated by MHC classes I and II, 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). Major histocompatibility complex and sexual selection has been observed in male mice making mate choices of females with different MHCs and thus demonstrating sexual selection. 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. The first descriptions of the MHC were made by British immunologist Peter Gorer in 1936. MHC genes were first identified in inbred mice strains. Clarence Little transplanted tumors across differing strains and found rejection of transplanted tumors according to strains of host versus donor. George Snell selectively bred two mouse strains, attained a new strain nearly identical to one of the progenitor strains, but differing crucially in histocompatibility—that is, tissue compatibility upon transplantation—and thereupon identified an MHC locus. For this work, Snell was awarded the 1980 Nobel Prize in Physiology or Medicine, together with Baruj Benacerraf and Jean Dausset. Of the three MHC classes identified, attention commonly focuses on classes I and II. By interacting with CD4 molecules on surfaces of helper T cells, MHC class II mediates establishment of specific immunity (also called acquired immunity or adaptive immunity). By interacting with CD8 molecules on surfaces of cytotoxic T cells, MHC class I mediates destruction of infected or malignant host cells, the aspect of specific immunity termed cellular immunity. (The other arm of specific immunity is humoral immunity, whose relation to MHC is more indirect.)