Neoantigen peptide–Major Histocompatibility Complex (pMHC) (Neoantigen-pMHC)

The neoantigen peptide–Major Histocompatibility Complex (pMHC) is a molecular assembly consisting of a tumor-specific mutant peptide bound to a Human Leukocyte Antigen (HLA) molecule on the surface of a cancer cell [1]. These complexes are central to the immune system's ability to distinguish malignant cells from healthy tissue, as they present mutations that are entirely absent from the normal proteome [3]. Therapeutic strategies targeting these complexes include personalized neoantigen vaccines, which prime the immune system to recognize these unique markers, and T-cell receptor-engineered (TCR-T) therapies that provide patients with T-cells pre-programmed to bind specific neoantigen-pMHCs [2][4]. Because neoantigens are derived from somatic mutations, they are highly specific to the tumor, potentially reducing the risk of autoimmune side effects compared to traditional tumor-associated antigens [3]. However, the low density of these complexes on the cell surface and the high degree of patient-specific variability present significant challenges for drug development [5]. Successful targeting of the neoantigen-pMHC complex is a cornerstone of modern precision oncology and personalized immunotherapy [4]. Sources: [1] https://www.nature.com/articles/s41568-017-0001-z [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301105/ [3] https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neoantigen [4] https://www.frontiersin.org/articles/10.3389/fimmu.2020.01610/full [5] https://pmc.ncbi.nlm.nih.gov/articles/PMC10045140/

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexMutant peptide-MHC complexTSA-pMHC

Engagement of the T-cell receptor (TCR) by the neoantigen-pMHC complex triggers a signaling cascade that leads to T-cell activation, proliferation, and the release of cytotoxic molecules like perforin and granzymes to induce apoptosis in the target tumor cell [1][2].