Neoantigen peptide-MHC class I complex (Neoantigen-MHC I)

Neoantigen peptide-MHC class I complexes are molecular assemblies on the surface of tumor cells consisting of a mutant peptide fragment bound to a Major Histocompatibility Complex (MHC) class I molecule. These neoantigens arise from somatic mutations, such as point mutations or frameshifts, which are entirely absent from the normal human proteome (Schumacher & Schreiber, 2015). The presentation of these complexes is a critical step for the adaptive immune system to identify and eliminate malignant cells via CD8+ cytotoxic T cells (Neefjes et al., 2011). Because neoantigens are not subject to central tolerance, they are highly immunogenic and represent ideal targets for precision oncology (Sahin & Türeci, 2018). Current therapeutic strategies include personalized mRNA or DNA vaccines and TCR-engineered T-cell therapies designed to recognize specific neoantigen-MHC pairings (Blankenstein et al., 2015). However, the effectiveness of these treatments can be limited by tumor heterogeneity and the ability of tumors to evade detection by downregulating MHC expression (Jhunjhunwala et al., 2021).

Other names

Other encoded neoantigen peptide-MHC class I complexes on tumor cellsTumor-specific antigen (TSA) complexNeoepitope-HLA complexMutant peptide-MHC complexTumor neoantigen

Therapeutic agents targeting these complexes function by inducing neoantigen-specific T-cell responses (vaccines) or by providing engineered T-cells (TCR-T) that recognize the specific peptide-MHC complex to trigger tumor cell lysis (Schumacher & Schreiber, 2015; Sahin & Türeci, 2018).