p53 R175H mutant peptide–HLA-A*02:01 complex

The p53 R175H mutant peptide–HLA-A*02:01 complex is a cell surface immune complex formed when a peptide derived from the most common missense mutation in TP53 (arginine to histidine at codon 175) is presented by the human leukocyte antigen HLA-A*02:01, a major histocompatibility complex class I (MHC-I) allele. This complex acts as a tumor-specific neoantigen: it is distinctively expressed on cancer cells harboring the TP53 R175H mutation and possessing the HLA-A*02:01 allele, but is not found on healthy cells. The complex serves as a potential immunotherapy target for T cell–based strategies, including TCR-mimic antibodies and bispecific antibodies, which are engineered to recognize the mutant peptide–MHC structure and redirect immune attack specifically to tumor cells. As such, it represents a highly selective, but technically challenging, target for cancer immunotherapy due to its low abundance and the specificity required to distinguish mutant from wild-type p53 peptide in the MHC context.

Other names

p53 R175H neoantigen–HLA-A*02:01 complexHLA-A*02:01–p53 R175H peptideMutant p53 R175H–HLA-A2 complex

Immune redirection: Bispecific antibodies (BsAbs) or engineered TCR-mimic antibodies bind the mutant peptide–HLA complex on the cell surface, simultaneously engaging T cells via anti-CD3 domains to trigger cytotoxicity against tumor cells presenting the neoantigen. T cell recognition: Engineered TCRs or TCR-like agents selectively recognize cells presenting the mutant p53 R175H peptide on HLA-A*02:01, facilitating immune cell–mediated killing.