Tumor protein p53 peptide–Human leukocyte antigen A*24 complex (p53-HLA-A*24)

The p53-derived peptide–HLA-A*24 complex is a specific peptide-major histocompatibility complex (pMHC) class I molecule that serves as a critical target for cancer immunotherapy. It consists of a peptide fragment derived from the tumor suppressor protein p53, which is frequently mutated or overexpressed in various malignancies, presented on the cell surface by the HLA-A*24 allele (particularly the A*24:02 subtype). This HLA allele is highly prevalent in East Asian populations, making this complex a significant target for regional precision medicine and the development of TCR-based therapies. In cancer cells, p53 mutations can lead to the presentation of neoantigens or the presentation of wild-type p53 peptides at levels significantly higher than in normal cells, creating a therapeutic window for immune intervention. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cells and bispecific antibodies designed to recognize the specific peptide-HLA configuration with high affinity. By binding to this complex, these therapies trigger a cytotoxic immune response specifically against the tumor cells. However, a major challenge remains the potential for cross-reactivity with normal tissues that express low levels of wild-type p53, necessitating high specificity in drug design.

Other names

p53-MHC class I complexp53-HLA-A24p53-derived peptide-MHC complexp53-HLA-A*24:02 complex

Therapeutic agents such as TCR-T cells or bispecific antibodies specifically recognize the p53 peptide fragment nested within the HLA-A*24 groove, triggering T-cell receptor signaling and subsequent cytotoxic lysis of the target tumor cell.