Major histocompatibility complex class I and II molecules presenting p53-derived peptides (p53-MHC complex)

The MHC class I and II molecules presenting p53-derived peptides serve as a vital interface for the immune system to detect intracellular oncogenic changes (Vogelstein et al., 2013). p53, encoded by the TP53 gene, is a tumor suppressor that is mutated in over 50% of human cancers, often leading to the presentation of unique neoantigens on the cell surface (Hsiue et al., 2021). These peptides are loaded onto MHC molecules and presented to T-cell receptors (TCRs), which can distinguish between mutant and wild-type sequences (Lo et al., 2020). This target is particularly attractive for immunotherapy because p53 mutations are often hotspot mutations shared across many patients, such as R175H, R248W, and R273H (Malekzadeh et al., 2019). Therapeutic interventions include TCR-engineered T cells (TCR-T) and bispecific antibodies (TCR-mimetics) that bind specifically to the p53-MHC complex (Hsiue et al., 2021). By targeting these complexes, clinicians aim to induce a potent and selective cytotoxic T-cell response against malignant cells. However, the low density of p53-MHC complexes on the cell surface and the potential for HLA downregulation by tumors present significant therapeutic hurdles (Lo et al., 2020). Ongoing research focuses on improving the affinity of TCR-based drugs and identifying the most immunogenic p53-derived peptides for vaccine development.

Other names

p53-HLA complexp53 peptide-MHC complexp53 neoantigen-MHC complexp53-pMHCTP53-MHC complex

T-cell receptor-mediated recognition of peptide-MHC complexes leading to T-cell activation and tumor cell lysis (Hsiue et al., 2021).