Mutant p53 peptide–MHC complex

The mutant p53 peptide–MHC complex is a cell surface molecular complex formed when intracellularly degraded mutant p53 proteins generate peptides that are processed and loaded onto major histocompatibility complex (MHC) class I molecules. These complexes are presented on the surface of tumor cells carrying TP53 mutations, particularly “hotspot” cancer-associated mutants such as p53 R175H[7][3]. While wild-type p53 is normally degraded and kept at low intracellular concentrations in healthy tissue, mutated forms often accumulate in tumors due to impaired regulation, leading to increased presentation of mutant-specific peptide—MHC complexes[3][7]. These complexes represent tumor-specific neoantigens and can be recognized by T cell receptors (TCRs) or by engineered antibody fragments (TCR-mimic antibodies), facilitating tumor-specific immune targeting without affecting normal tissues[7][3][2]. This makes the mutant p53 peptide–MHC complex a promising and specific immunotherapeutic target under development for adoptive TCR therapy, bispecific antibodies, and TCR-mimic antibody therapeutics in cancers harboring TP53 mutations[3][7][6].

Other names

p53 mutant peptide–MHC complexTP53 mutant peptide–MHC complexMutant p53 neoantigen–MHC complex

Targeted immune cell recruitment and activation via recognition of the mutant p53 peptide presented on MHC class I molecules by T cell receptor or TCR-mimic antibody[3][7]. Antibody-dependent cellular cytotoxicity (ADCC) and T cell-mediated killing of tumor cells presenting the mutant p53 peptide–MHC complex[6][7].