p53-derived peptide–HLA-A*02:01 complex (p53/HLA-A*02:01)

The p53-derived peptide–HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) class I molecule that serves as a critical neoantigen or tumor-associated antigen target in cancer immunotherapy. It consists of a peptide fragment derived from the p53 tumor suppressor protein—often containing common hotspot mutations like R175H—bound to the HLA-A*02:01 allele, which is highly prevalent in human populations (PubMed: 31413067). In healthy cells, p53 levels are typically low and peptides are not presented at levels sufficient for T-cell activation; however, in many cancers, p53 is mutated or overexpressed, leading to the presentation of these specific complexes on the cell surface (Nature Communications, 2021). This complex is targeted by various therapeutic modalities, including T-cell receptor (TCR) engineered T-cells, TCR-mimic antibodies, and bispecific T-cell engagers. These therapies aim to redirect the immune system to recognize and eliminate malignant cells displaying the p53/HLA-A*02:01 signature. Challenges in targeting this complex include the low density of pMHC on the cell surface and the potential for off-target reactivity against wild-type p53 in normal tissues (Frontiers in Immunology, 2020).

Other names

p53-MHC class I complexp53-HLA-A2 complexp53 peptide-HLA-A*02:01p53(264-272)/HLA-A*02:01p53-R175H/HLA-A*02:01 complex

Recognition of the specific p53 peptide presented in the HLA-A*02:01 groove by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to targeted cytotoxic T-lymphocyte (CTL) mediated lysis of the tumor cell.