Patient-specific tumor antigen–peptide–major histocompatibility complex (pMHC)

Patient-specific tumor antigen–peptide–MHC (pMHC) complexes are unique molecular signatures presented on the surface of malignant cells, resulting from somatic mutations that create novel, non-self peptides known as neoantigens (Nature Reviews Cancer, 2021). These complexes are formed when neoantigenic peptides are processed and loaded onto Major Histocompatibility Complex (MHC) molecules, allowing the immune system to distinguish tumor cells from healthy tissue (Frontiers in Immunology, 2020). The primary biological function of these complexes is to serve as the recognition element for T-cell receptors (TCRs), triggering a targeted immune response (Cell, 2019). In clinical practice, they are the primary targets for personalized cancer vaccines and TCR-engineered T-cell therapies, which are designed to exploit the high specificity of neoantigens to minimize off-target effects (Journal of Hematology & Oncology, 2023). Despite their potential, therapeutic success can be limited by tumor heterogeneity and the ability of cancer cells to downregulate MHC expression to evade immune detection (Nature Communications, 2022).

Other names

Neoantigen-MHC complexTumor-specific antigen-MHC complexNeoepitope-HLA complexTSA-MHC complexPatient-specific pMHC

MHC-restricted T-cell receptor (TCR) binding and activation of cytotoxic T-lymphocytes (CTLs) leading to tumor cell lysis.