Peptide–major histocompatibility complex (peptide–MHC) (pMHC)

A peptide–major histocompatibility complex (peptide–MHC, pMHC) is a molecular complex formed when a short peptide fragment (typically 8–25 amino acids) is bound and presented on the cell surface by a major histocompatibility complex (MHC) molecule[2][1][5][4]. These complexes are recognized by T cell receptors (TCRs) on T lymphocytes, which form the basis for the adaptive immune system’s ability to detect infected, malignant, or otherwise altered cells[1][2][3][4][6]. Tumor-specific pMHC complexes are generated when intracellular proteins derived from tumor-specific mutations (neoantigens) or viral proteins are processed and loaded onto MHC molecules, particularly on cancer cells, enabling immune recognition and targeted destruction by T cells[3][4][7]. Therapeutic targeting of tumor-specific pMHC has become a cornerstone in cancer immunotherapy, enabling engineerable precision medicines, but presents challenges related to the complexity and variability of peptide presentation, immune escape, and safety risks such as autoimmunity[3][4][7].

Other names

Major histocompatibility complex–peptide complexPeptide–MHC complexpMHC complexPeptide–HLA complex (in human context)Antigen–MHC complex

Enhancement or inhibition of T cell recognition of pMHC (by increasing or blocking TCR-pMHC interactions) Stimulation of antitumor immune response via presentation of tumor-specific peptides on MHC (known as neoantigen targeting) Immune checkpoint blockade increases T cell response against pMHC-presenting cells