HLA-A*02:01-p53 (264-272) complex (HLA-A2/p53(264-272))

The HLA-A*02:01-p53 (264-272) complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of cells, particularly cancer cells that overexpress the tumor suppressor protein p53 [1, 8]. The peptide, with the sequence LLGRNSFEV, represents an immunodominant epitope derived from the wild-type p53 protein [2, 9]. In many cancers, p53 is mutated or stabilized, leading to its accumulation and subsequent increased presentation of this epitope on the cell surface via the HLA-A*02:01 allele [1, 5]. This complex serves as a critical target for various immunotherapies, including T-cell receptor (TCR)-based therapies, TCR-like antibodies, and peptide vaccines, which aim to direct the immune system to selectively kill tumor cells [1, 4, 7]. However, therapeutic challenges include the potential for "on-target, off-tumor" toxicity due to low-level p53 expression in normal tissues and the emergence of tumor escape mechanisms such as the R273H mutation, which can interfere with the processing and presentation of the 264-272 epitope [5, 6]. Additionally, the clinical utility of targeting this complex is restricted to patients who carry the HLA-A*02:01 allele [1, 13].

Other names

p53(264-272)/HLA-A*02:01LLGRNSFEV-HLA-A2 complexp53 peptide-MHC complexHLA-A*02:01-p53(aa264-272)p53 R264-272 epitope

The complex is recognized by specific T-cell receptors (TCRs) or TCR-like antibodies, which bind to the peptide-MHC interface to initiate cytotoxic T-lymphocyte (CTL) activation and subsequent lysis of the tumor cell [1, 8].