Neoantigen-Major Histocompatibility Complex class I (NeoAg-MHC I)

The Neoantigen-Major Histocompatibility Complex (MHC) class I complex is a critical immunological target formed when somatic mutations in a tumor cell's genome result in novel, non-self protein sequences that are processed and displayed on the cell surface [1]. These complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells, serving as the primary signal for the immune system to distinguish malignant cells from healthy tissue [2]. Because neoantigens are absent from the normal proteome, they are not subject to central thymic tolerance, making them ideal targets for highly specific immunotherapies such as personalized cancer vaccines and TCR-engineered T-cell (TCR-T) therapies [3]. Therapeutic strategies aim to either prime the endogenous immune system to recognize these unique peptide-MHC signatures or provide exogenously engineered T cells with high affinity for specific neoepitopes [4]. However, the clinical utility of targeting these complexes is often challenged by the high degree of HLA polymorphism in the human population and the ability of tumors to evade detection through the loss of MHC expression or defects in the antigen-processing machinery [5].

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexpHLA complexNeoantigen-HLA-A/B/C complexMHC-I-restricted neoantigen

Induction of antigen-specific CD8+ T-cell responses through the presentation of tumor-specific mutated peptides on MHC class I molecules to activate cytotoxic T-cell receptors [1][2].