Human leukocyte antigen A*02 presenting p53-derived peptides (HLA-A*02:p53)

The HLA-A*02 presenting p53-derived peptides complex is a critical immunological target in oncology, representing the presentation of intracellular tumor-suppressor protein fragments on the cell surface. In many cancers, the TP53 gene is mutated, leading to the presentation of neoantigens or overexpressed wild-type peptides by the Major Histocompatibility Complex (MHC) Class I molecule, specifically the HLA-A*02 allele (Hsiue et al., 2021, Science). This complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T cells, triggering an immune response against the cancer cell (Lo et al., 2020, JCI). Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies (TCR-T) and TCR-mimetic bispecific antibodies that bridge the peptide-MHC complex with T cells. Because p53 mutations are among the most common genetic alterations in human cancers, this target offers a pathway for highly specific immunotherapy. However, challenges include the low density of these complexes on the cell surface and the potential for cross-reactivity with similar self-peptides (Vogelstein et al., 2021, Science).

Other names

HLA-A*02:01/p53 complexp53-HLA-A2 complexMHC-p53 peptide complexp53 neoantigen-HLA complexp53-derived peptide-MHC class I complex

T-cell receptor (TCR) engagement or TCR-mimetic antibody binding to the peptide-MHC complex, leading to T-cell mediated lysis of the target cell.