Wild-type p53 (168-176) peptide–HLA-A*02:01 complex (WT p53-R175/A2 complex)

The wild-type p53 R175 peptide–HLA-A*02:01 complex consists of a 9-amino acid peptide (HMTEVVRRC) derived from the wild-type tumor suppressor protein p53, presented by the human leukocyte antigen (HLA) allele A*02:01. This complex is found on the surface of both normal and malignant cells that express the p53 protein. In modern oncology, it is primarily characterized as a critical off-target for precision immunotherapies, such as bispecific T-cell engagers (e.g., CLSP-1025) and T-cell receptor (TCR) therapies, which are engineered to target the R175H missense mutation. Because the wild-type peptide differs from the R175H mutant peptide by only a single amino acid (Arginine vs. Histidine at position 175), the wild-type complex is used in rigorous screening to ensure that therapeutic agents do not cross-react with healthy cells. While some historical p53 vaccines have targeted wild-type sequences due to p53 overexpression in tumors, the high risk of systemic toxicity makes the wild-type complex a major safety hurdle rather than a primary therapeutic target in neoantigen-based strategies.

Other names

p53(168-176)/HLA-A*02:01HMTEVVRRC/HLA-A*02:01Wild-type p53 R175 neoantigen-counterpartp53 R175 wild-type peptide-MHC complex

This complex serves as a negative control or off-target for immunotherapies (such as bispecific antibodies and TCR-T cells) designed to specifically recognize the mutant p53 R175H neoantigen.