Peptide–Major Histocompatibility Complex (pMHC) (pMHC)

The peptide–Major Histocompatibility Complex (pMHC) on tumor cells is a molecular assembly consisting of a short peptide fragment, derived from intracellular proteins, bound within the groove of an MHC molecule (typically MHC Class I in humans, also known as HLA) [1.1.1, 1.3.1]. This complex serves as the primary mechanism for the immune system to monitor the internal state of a cell; in malignant cells, pMHCs present tumor-associated antigens (TAAs) or neoantigens that are recognized by T-cell receptors (TCRs) on cytotoxic T lymphocytes [1.1.3, 1.3.2]. This recognition is the fundamental step in the adaptive immune response against cancer [1.5.3]. Modern immunotherapies, such as TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers like Tebentafusp, are designed to specifically target these pMHC complexes, allowing for the destruction of tumor cells that do not express traditional surface biomarkers [1.3.2, 1.4.2]. However, the effectiveness of these therapies is often limited by the high polymorphism of HLA genes (HLA restriction) and the ability of tumors to downregulate MHC expression as a means of immune evasion [1.2.4, 1.5.3].

Other names

MHC-peptide complexHLA-peptide complexAntigen-MHC complexpMHC complexTumor-specific pMHC

Engineered T-cell receptors (TCRs) or TCR-like antibodies bind to the specific peptide-MHC complex on the tumor cell surface, triggering T-cell activation and the release of cytotoxic granules (perforin and granzymes) to induce apoptosis in the target cell.