The major histocompatibility complex (MHC) (also called human leukocyte antigens, HLAs) is the mechanism by which the immune system is able to differentiate between self and nonself cells. The MHC is a collection of glycoproteins (proteins with a carbohydrate) that exist on the plasma membranes of nearly all body cells. The proteins of a single individual are unique, originating from 20 genes, with more than 50 variations per gene between individuals. Thus, it is extremely unlikely that two people, except for identical twins, will possess cells with the same set of MHC molecules.
The immune system is able to identify nonself cells by aberrations in the MHC displayed on the plasma membrane. There are two groups of MHC molecules, and each group generates different markings on the plasma membrane:
MHC‐I glycoproteins are produced by all body cells (except red blood cells). When a cell becomes cancerous or is invaded by a virus, unfamiliar proteins are synthesized in the cell. These proteins are endogenous antigens—that is, antigens produced inside the cell. Portions of these antigens are combined with MHC‐I glycoproteins and, when displayed on the plasma membrane, indicate a nonself cell.
MHC‐II glycoproteins are produced only by antigen‐presenting cells (APCs)—mostly macrophages and B cells. APCs actively ingest exogenous antigens—antigens that originate outside the cell. Exogenous antigens include viruses, toxins, pollen, or bacteria that are circulating in the blood, lymph, or body fluids. APCs break down the antigens and incorporate pieces of them with MHC‐II glycoproteins. This aberrant display of MHC markers is recognized as nonself.