Tumor neoantigen peptide–major histocompatibility complex complex

The tumor neoantigen peptide–major histocompatibility complex (MHC) complex is a molecular complex formed when a short peptide (“neoantigen”) generated by somatic mutations or aberrant post-translational modifications in tumor cells is bound and presented on the cell surface by an MHC class I or class II molecule[1][6]. These neoantigen–MHC complexes are recognized by T cell receptors (TCRs) on cytotoxic CD8+ (for class I) or helper CD4+ (for class II) T cells, initiating an immune response that can result in targeted tumor cell destruction[1][2][4]. Because tumor neoantigens are not found in normal tissue, they are highly specific targets for cancer immunotherapy, including personalized cancer vaccines, adoptive T cell therapies, and TCR-mimic antibody drugs[3][5][6]. A key challenge is that tumor cells may downregulate MHC expression or lose the antigen presentation machinery, contributing to therapeutic resistance and immune evasion[1][3]. The structural features of the peptide–MHC complex, including peptide sequence, binding affinity, and modifications, are critical determinants of immunogenicity and therapy success[2][4][5][6].

Other names

tumor neoantigen-MHC complextumor neoantigen pMHC complexneoantigen peptide-MHC complexneoepitope-MHC complex

Recognition and elimination of tumor cells by cytotoxic T lymphocytes via TCR engagement with neoantigen–MHC complex[1][4][5] Activation of T cells through bispecific antibodies or adoptive T cell transfer targeting specific pMHC complexes[5] Presentation of post-translationally modified or mutated tumor peptides to the immune system for targeted tumor cell killing[6]