Major histocompatibility complex molecules (MHC molecules)

Major histocompatibility complex (MHC) molecules are glycoproteins expressed on the surface of cells that play a central role in adaptive immunity by presenting peptide fragments derived from proteins—both self and foreign—to T lymphocytes. This process enables the immune system to distinguish between self-cells and infected or abnormal cells. There are two primary classes: 1. *MHC Class I* molecules consist of a polymorphic alpha chain anchored in the membrane plus β2-microglobulin. They present endogenous peptides—typically from cytosolic proteins such as viral or tumor antigens—to CD8+ cytotoxic T lymphocytes. These molecules are expressed on nearly all nucleated cells. 2. *MHC Class II* molecules consist of two polymorphic chains (alpha and beta), both encoded within the MHC region on chromosome 6. They present exogenous peptides processed from extracellular proteins internalized by specialized antigen-presenting cells like dendritic cells, macrophages, and B lymphocytes to CD4+ helper T lymphocytes. The interaction between peptide-MHC complexes and specific T-cell receptors triggers activation or tolerance depending on whether presented peptides represent self or non-self antigens. The extensive polymorphism within human populations ensures broad coverage against diverse pathogens but also underlies challenges such as transplant rejection and susceptibility to autoimmune diseases linked with particular alleles like HLA-B27. Overall, MHC molecules serve as essential mediators bridging innate cellular processes with adaptive immune recognition mechanisms critical for host defense.

Other names

Human leukocyte antigens (HLA, in humans)MHC class IMHC class IIHLA-AHLA-BHLA-C (class I)HLA-DRHLA-DPHLA-DQ (class II)

Drugs targeting pathways involving MHC may: Modulate antigen processing/presentation. Alter T cell activation thresholds. These mechanisms are indirect rather than direct binding to the MHC molecule itself.