Tumor neoantigen–Major Histocompatibility Complex class I complex (Neoantigen-MHC I complex)

Tumor neoantigen–MHC class I complexes are molecular assemblies formed by the association of a tumor-specific mutated peptide (neoantigen) with a Major Histocompatibility Complex (MHC) class I molecule. When these complexes are displayed on the surface of Antigen-Presenting Cells (APCs), such as dendritic cells, they serve as the primary signal for the activation of naive CD8+ T cells through the process of cross-presentation [1, 2]. Because neoantigens result from somatic mutations unique to the tumor genome, these complexes are absent from healthy tissues, providing an ideal target for highly specific cancer immunotherapies [1]. Current therapeutic strategies, including personalized neoantigen vaccines (mRNA or peptide-based), aim to enhance the presentation of these complexes on APCs to elicit a robust, tumor-specific T-cell response [2, 3]. Additionally, TCR-engineered T-cell therapies are being developed to recognize specific neoantigen-MHC combinations with high affinity. The clinical success of targeting these complexes depends on accurate neoantigen prediction, the patient's HLA profile, and the ability of the immune system to overcome the immunosuppressive tumor microenvironment [3, 4].

Other names

Neoepitope-MHC I complexMutated peptide-HLA class I complexTumor-specific antigen-MHC complexpHLA complexNeoantigen-HLA complex

Therapeutic vaccines deliver neoantigen-encoding sequences to Antigen-Presenting Cells (APCs), which process and present them as MHC class I complexes to prime and activate neoantigen-specific CD8+ T cells. These activated T cells then circulate and recognize the same complexes on tumor cells, leading to targeted lysis.