Patient-specific neoantigen peptide–major histocompatibility complex class I (Neoantigen-pMHC-I)

Patient-specific neoantigen peptide–major histocompatibility complex class I (pMHC-I) complexes are unique molecular targets formed when mutated protein fragments from tumor cells are processed and presented on the cell surface by HLA class I molecules (Schumacher & Schreiber, 2015, Science). These neoantigens arise from somatic mutations—such as single nucleotide variants, insertions, or deletions—that are unique to the patient's tumor and absent in healthy tissues (Sahin & Türeci, 2018, Science). This exclusivity makes them ideal targets for precision immunotherapy, as it allows the immune system to distinguish between malignant and normal cells with high fidelity. Therapeutic interventions, including personalized mRNA or peptide vaccines and TCR-engineered T-cell (TCR-T) therapies, aim to exploit these complexes to induce a robust CD8+ cytotoxic T-cell response (Blass & Ott, 2021, Nature Reviews Clinical Oncology). The successful recognition of the pMHC-I complex by a T-cell receptor (TCR) triggers the release of perforins and granzymes, leading to the selective destruction of the tumor cell. However, challenges such as HLA loss or downregulation by the tumor and the potential for cross-reactivity with self-peptides remain significant hurdles in the clinical application of these therapies (Yadav et al., 2014, Nature).

Other names

Neoepitope-HLA complexTumor-specific neoantigen-MHC complexPersonalized neoantigen-MHC class I complexTSA-MHC complexNeoantigen-pMHC complex

Recognition by T-cell receptors (TCRs) on CD8+ T cells, leading to the induction of a targeted cytotoxic immune response and apoptosis of the tumor cell.