pMHC

pMHC stands for peptide-major histocompatibility complex. It refers to the complex formed when a peptide antigen binds in the groove of an MHC molecule and is displayed on the surface of antigen-presenting cells. The pMHC complex is the primary unit recognized by T cell receptors, enabling specific immune surveillance of intracellular and extracellular proteins.

MHC class I and class II molecules form distinct pMHC complexes with different peptide repertoires and T cell targets. Class I pMHC typically presents short peptides, about 8 to 11 amino acids, derived from intracellular proteins to CD8+ T cells. Peptide generation involves proteasomal degradation and cytosolic transport into the endoplasmic reticulum, where loading occurs with assistance from transporters associated with antigen processing. Class II pMHC presents longer peptides, usually from exogenous or endocytosed proteins, to CD4+ T cells. Invariant chain blocks premature binding in the ER, and loading in late endosomes is aided by CLIP and HLA-DM in humans.

Functionally, the T cell receptor recognizes a specific pMHC complex, triggering signaling that can lead to T cell activation, cytokine production, and, in the case of CD8+ T cells, cytotoxic responses. The stability and affinity of the pMHC–TCR interaction influence the outcome of the response.

pMHC is a central focus of immunology research and clinical applications. Tools such as pMHC tetramers enable detection and characterization of antigen-specific T cells, while pMHC-based vaccines and immunotherapies are areas of active development. The repertoire of pMHCs is shaped by MHC polymorphism, peptide binding affinity, and peptide processing, all contributing to individual immune recognition.