Tumor neoantigen–Major Histocompatibility Complex (MHC) (Neoantigen-MHC)

Tumor neoantigen–Major Histocompatibility Complex (MHC) complexes are specialized molecular structures on the surface of malignant cells that present mutated peptide fragments to the immune system. These complexes are formed when proteins containing somatic mutations—unique to the tumor and absent in healthy tissue—are degraded by the proteasome and loaded onto MHC Class I or II molecules (Schumacher & Schreiber, 2015, Science). Because these neoantigens are not subject to central thymic tolerance, they are highly immunogenic and can be recognized by T-cell receptors (TCRs) as non-self, triggering a potent cytotoxic immune response (Blass & Ott, 2021, Nature Reviews Clinical Oncology). In modern oncology, these complexes are the primary targets for personalized cancer vaccines and adoptive cell therapies, such as TCR-engineered T cells, which aim to exploit the specificity of the neoantigen-MHC interaction (Sahin & Türeci, 2018, Science). The therapeutic goal is to direct the patient's immune system to selectively destroy tumor cells while minimizing damage to normal tissues. However, the clinical efficacy of targeting these complexes can be hindered by tumor-mediated immune evasion mechanisms, such as the loss of HLA expression or the development of a suppressive tumor microenvironment (Gubin et al., 2015, Journal of Clinical Investigation).

Other names

Neoepitope-MHC complexpeptide-HLA complexpHLATumor-specific antigen-MHC complexTSA-MHC complexNeoantigen-HLA complex

T-cell receptor (TCR) mediated recognition and induction of antigen-specific cytotoxic T lymphocyte (CTL) response