Major Histocompatibility Complex (MHC) Proteins Are Considered the Centrai Regulators of the Immune System

Activation of specific T cells is highly dependent on interactions with major histocompatibility complex (MHC) proteins, which have a unique ability to bind to processed antigenic peptides.

red to as the MHC locus. The MHC gene complex is inherited as a block of genes and is known to encode three categories of proteins or antigens: class I, class II, and class III antigens. The number of genes that encode class I antigens varies from species to species, with a large number in humans (>30) at one end of the spectrum to a limited number of genes in pigs, turkeys, and cheetahs at the other end. In general, all nucleated cells express ClassIantigen, which is a single α-chain peptide of approximately 45 kilodaltons (kD) linked to β₂-microglobulin (a non-MHC protein thought to be essential for proper folding and stabiliza­tion of the α chain). Class I antigens can bind to peptides (e.g., viral peptides) and serve as receptors for CD8 molecules on cyto­toxic T cells. Class I antigens have a high rate of mutation, but no recombination. These mutations allow class I antigens to alter their ability to bind to endogenous, processed antigenic peptides.