p53 peptide-Major Histocompatibility Complex class I complex (p53-MHC I)

The p53 peptide-Major Histocompatibility Complex (MHC) class I complex is a molecular assembly consisting of a peptide fragment derived from the tumor suppressor protein p53 presented on the cell surface by MHC class I molecules (Hsiue et al., 2021, Science). In malignant cells, p53 is frequently mutated or overexpressed, resulting in the presentation of these peptides at levels significantly higher than in normal tissues, or the presentation of unique neoantigenic sequences (Vogelstein et al., 2013, Science). This complex serves as a critical recognition element for the cellular immune system, specifically CD8+ cytotoxic T cells, which identify the p53-pMHC through their T-cell receptors (TCRs). On dendritic cells, these complexes are essential for the cross-presentation of tumor antigens to prime naive T cells, while on tumor cells, they serve as the direct target for immune-mediated destruction (Lo et al., 2020, Clinical Cancer Research). Therapeutic interventions targeting this complex include TCR-engineered T cells (TCR-T), TCR-like (TCRm) antibodies, and bispecific T-cell engagers (BiTEs) designed to bypass natural immune tolerance and selectively eliminate p53-altered cancer cells (Hsiue et al., 2021). The specificity of these therapies often depends on the patient's HLA genotype, most commonly HLA-A*02:01, and the specific p53 mutation present in the tumor.

Other names

p53-HLA complexp53-pMHCp53-HLA-A*02:01 complexp53 neoantigen-MHC complexp53-derived peptide–MHC class I complex on dendritic cells and tumor cells

T-cell receptor-mediated recognition and subsequent T-cell induced lysis of target cells