peptideMHC

Peptide-MHC (pMHC) complexes form when a peptide antigen binds to a major histocompatibility complex (MHC) molecule, and are displayed on the surface of nearly all nucleated cells. These complexes are central to adaptive immunity, because they are recognized by T cell receptors (TCRs) on CD4+ and CD8+ T cells, enabling the immune system to distinguish self from non-self and to respond to pathogens or abnormal cells.

MHC class I molecules present short peptides (typically 8-11 amino acids) to CD8+ T cells, whereas MHC class II molecules present longer peptides (often 12-25 amino acids) to CD4+ T cells. The peptide binds in a groove formed by the MHC molecule, with certain residues acting as anchor residues that determine binding affinity. The combination of MHC polymorphism and peptide sequence determines the repertoire of pMHC ligands that can be displayed by a cell.

In humans, the class I pathway uses proteasomal degradation of cytosolic proteins, transport of peptides into the endoplasmic reticulum by TAP, and loading onto MHC I with help from chaperones, followed by surface expression. The class II pathway involves uptake of extracellular proteins into endosomes/lysosomes, proteolytic processing, and peptide loading aided by HLA-DM in specialized compartments before surface expression.

pMHC recognition by TCRs drives T cell activation, tolerance, and memory. The diversity of pMHC shapes transplantation compatibility, vulnerability to infections, and responses to vaccines and cancer immunotherapy. Research tools include pMHC tetramers and multimers that label antigen-specific T cells, and structural and computational methods to study binding.