Neoantigen peptide–Major Histocompatibility Complex (neoAg-MHC) (neoAg-MHC)

Neoantigen peptide–Major Histocompatibility Complex (neoAg-MHC) complexes are unique molecular signatures found on the surface of tumor cells, resulting from somatic mutations that create novel, non-self protein sequences. These mutant peptides are processed by the cellular proteasome and loaded onto MHC class I or II molecules for presentation to the immune system (Schumacher & Schreiber, Science, 2015). Unlike tumor-associated antigens, neoantigens are strictly tumor-specific, meaning they are not expressed in healthy tissues, which minimizes the risk of central tolerance and off-target autoimmune toxicity (Blass & Ott, Nature Reviews Clinical Oncology, 2021). They serve as the primary targets for various immunotherapies, including personalized cancer vaccines, TCR-engineered T-cell (TCR-T) therapies, and neoantigen-specific bispecific antibodies (Xie et al., Frontiers in Immunology, 2023). By specifically recognizing these complexes, the immune system can distinguish malignant cells from normal cells with high precision. However, challenges remain regarding the identification of driver neoantigens and the potential for tumor escape through MHC downregulation or loss of the neoantigen itself (Sahin & Türeci, Science, 2018).

Other names

Tumor-specific neoantigen-HLA complexNeoepitope-MHC complexMutant peptide-MHC complexTSA-MHC complex

Recognition of tumor-specific mutant peptides presented on MHC molecules by T-cell receptors (TCRs), triggering cytotoxic T-lymphocyte activation and tumor cell lysis (Schumacher & Schreiber, Science, 2015).