p53 peptide–major histocompatibility complex class I complex

The p53 peptide–major histocompatibility complex class I complex is a cellular surface structure consisting of endogenous peptides derived from the p53 tumor suppressor protein (wild-type or mutant) presented on class I MHC/HLA molecules. Mutant forms of p53 commonly accumulate in cancer cells due to disrupted degradation, resulting in higher levels of p53-derived peptides presented by MHC class I molecules, particularly alleles such as HLA-A*24:02 and HLA-A*02:01[3][4][5]. These complexes can be recognized by cytotoxic T cells as "neoantigens," distinguishing cancer cells from normal cells[2][3][5]. Due to their tumor specificity, especially when the peptide contains a recurrent cancer-associated mutation (such as R175H or Y163C), the p53 peptide–MHC complex has emerged as a novel immunotherapy target. Therapeutic agents (bispecific antibodies, TCR-like antibodies, engineered TCRs) are being developed to engage T cells and direct cytotoxicity towards tumor cells presenting these complexes, overcoming the "undruggable" nature of p53 and broadening the reach of precision immuno-oncology therapies[3][5][6][7]. Identification and targeting require knowledge of the patient's HLA type and tumor p53 mutation status. The major challenges include specificity (to avoid harming normal tissues with similar peptides), low antigen density, and HLA restriction.

Other names

p53–peptide/MHC complexp53–peptide–MHC class I complexp53–peptide–HLA complexp53 pMHC complexmutant p53–MHC complexTP53–peptide/MHC complex

Redirects T cell–mediated cytotoxicity to cells displaying p53-derived neoantigens on MHC class I[3][5][6] Immune checkpoint (antigen-specific) targeting[5] Recognition and destruction of mutant p53-expressing tumor cells by engineered antibodies or T cell receptors[3][5]