Tumor-associated peptide–major histocompatibility complex complex

A **tumor-associated peptide–major histocompatibility complex (pMHC) complex** is a molecular structure in which a short peptide, derived from tumor-associated proteins (including mutated, overexpressed, or posttranslationally modified proteins such as phosphopeptides), is bound and presented on the cell surface by a host major histocompatibility complex (MHC) molecule[2][6]. These complexes are central to the adaptive immune response, enabling T cells to discriminate between healthy and tumor cells. Tumor-associated pMHC complexes are highly relevant therapeutic targets for cancer immunotherapy, as their presence can elicit specific recognition and killing of tumor cells by T cells engineered or selected for high-affinity binding to the tumor-specific peptide–MHC structure[2][6]. Their structure, abundance, and antigenic specificity determine immune surveillance efficacy and therapeutic potential, but also present challenges including antigenic heterogeneity, potential autoimmunity, and immune evasion by tumors[6][7]. The canonical recognition mode for T cell receptors involves direct contacts with both the MHC molecule and the presented peptide, and these complexes can be targeted by emerging therapies such as TCR-engineered T cells or TCR-mimic antibodies[6][2].

Other names

Tumor pMHC complexTumor antigen–MHC complexTumor antigen–peptide–MHC complexTumor-associated peptide–MHCCancer peptide–MHC

T-cell receptor targeting (therapies recognize and bind tumor-associated pMHC on tumor cells, leading to immune-mediated killing); Immune checkpoint modulation (checkpoint inhibitors may enhance T cells targeting tumor pMHC)