Neoantigen-MHC complex (pMHC) (pMHC)

The Neoantigen-MHC complex is a molecular assembly consisting of a tumor-specific mutated peptide (neoantigen) bound to a Major Histocompatibility Complex (MHC) molecule on the cell surface. This complex is the fundamental unit of recognition for the adaptive immune system, specifically for T-cell receptors (TCRs) on CD8+ and CD4+ T cells (Schumacher & Schreiber, 2015) [1]. Because neoantigens arise from non-synonymous somatic mutations unique to cancer cells, they are not present in the normal proteome, making the Neoantigen-MHC complex an ideal target for highly specific immunotherapy with minimal risk of central tolerance or autoimmunity (Hacohen et al., 2013) [2]. Therapeutic interventions targeting these complexes include personalized neoantigen vaccines, such as mRNA-4157, which aim to expand the patient's endogenous T-cell repertoire, and adoptive cell therapies using TCR-engineered T cells (TCR-T) designed to bind specific neoepitopes with high affinity (Ott et al., 2017) [3]. However, challenges remain, including the heterogeneity of neoantigen expression within tumors and the potential for immune escape through the downregulation of MHC molecules or other components of the antigen processing machinery (Sahin & Türeci, 2018) [4].

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexPatient-specific neoantigen-MHC complexpMHC complexTSA-MHC complex

Therapeutic agents either deliver the neoantigen to stimulate endogenous T-cell expansion (vaccines) or provide engineered T-cells (TCR-T) that directly bind the neoantigen-MHC complex, triggering a cytotoxic immune response against cells presenting the specific mutation.