Antigen-specific peptide–major histocompatibility complex (MHC) complex (pMHC complex)

The **antigen-specific peptide–MHC complex** consists of a peptide antigen bound in the groove of a major histocompatibility complex (MHC) molecule and is presented on the surface of antigen-presenting cells or any nucleated cell (class I). The peptide is derived from either intracellular (class I) or extracellular (class II) proteins and is presented by MHC molecules encoded by highly polymorphic genes. Recognition of specific pMHC complexes by T cell receptors (TCRs) is essential for triggering adaptive immunity, determining the specificity of the T cell response, and enforcing MHC restriction. The vast diversity of peptide–MHC combinations underlies individual differences in immune response, tolerance, and susceptibility to autoimmune diseases. Therapeutically, engineered TCRs or protein binders targeting pMHC complexes have enabled highly specific immunotherapies against cancer and infectious diseases, but present challenges including HLA polymorphism, adequate antigen selection, and potential for off-target effects[1][2][3][4][5][6][7].

Other names

peptide–MHC complexpeptide–HLA complex (in humans)pMHCantigenic peptide–MHC complex

Drugs/biologics targeting pMHC complexes act via modifying antigen presentation, selectively engaging T cells able to recognize the complex, or redirecting immune specificity[3] TCR mimetics and engineered receptors bind the pMHC complex, triggering immune effector functions (e.g. cytotoxicity) Modulation or blockade of antigen presentation in autoimmune disease