Neoantigen peptide–Major Histocompatibility Complex class I (pMHC-I complex)

The Neoantigen peptide–Major Histocompatibility Complex class I (pMHC-I) complex is a molecular assembly found on the surface of tumor cells, consisting of a tumor-specific mutant peptide (neoantigen) bound to an HLA class I molecule. These neoantigens arise from somatic mutations in the cancer genome, such as point mutations, insertions, or deletions, making them unique to the tumor and absent in healthy tissues. The primary biological function of the pMHC-I complex is to present these intracellular 'foreign' signals to the immune system, specifically to CD8+ cytotoxic T lymphocytes. Recognition of the pMHC-I complex by a cognate T-cell receptor (TCR) triggers an immune response aimed at destroying the malignant cell. In the context of modern oncology, this complex is a premier therapeutic target for personalized medicine, including neoantigen vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-mimetic bispecific antibodies. Because neoantigens are highly specific to the tumor, targeting the pMHC-I complex offers the potential for high therapeutic efficacy with minimal damage to normal cells, although challenges such as HLA loss and peptide-level cross-reactivity remain significant hurdles.

Other names

Neoantigen-MHC-I complexNeoepitope-HLA complexTumor-specific antigen-MHC complexMutant peptide-MHC complexpMHC-I

T-cell receptor (TCR) binding, Bispecific T-cell engager (BiTE) binding, Vaccine-induced T-cell priming, TCR-mimetic antibody binding