Tumor-associated peptide–Major Histocompatibility Complex (pMHC) (pMHC)

Tumor-associated peptide–Major Histocompatibility Complex (pMHC) complexes represent the molecular interface between cancer cells and the adaptive immune system. These complexes consist of a peptide fragment, derived from tumor-specific or tumor-associated proteins, presented within the binding groove of an MHC molecule on the cell surface (Rock et al., 2016). Marrow-infiltrating lymphocytes (MILs) are a distinct population of T cells residing in the bone marrow that possess T-cell receptors (TCRs) specifically evolved to recognize these pMHC targets (Noonan et al., 2015). Unlike peripheral blood lymphocytes, MILs are enriched for central memory T cells and exhibit a broad polyfunctional response against multiple tumor antigens, making their TCR-pMHC interactions highly effective for therapeutic exploitation (Borrello & Noonan, 2016). In clinical applications, MILs are harvested, expanded ex vivo, and re-infused into patients to treat malignancies like multiple myeloma, where they target the diverse pMHC landscape of the tumor. Additionally, the specific TCR sequences from MILs can be used to engineer TCR-T cell therapies or bispecific molecules designed to bind these pMHC complexes with high precision.

Other names

Tumor-associated antigen-MHC complexHLA-peptide complexT-cell epitopepMHC complexMHC-peptide complex

T-cell receptor (TCR) recognition of the pMHC complex leads to the formation of an immunological synapse, triggering downstream signaling (e.g., CD3 zeta chain phosphorylation) that results in the release of perforins and granzymes to induce target cell apoptosis (Rock et al., 2016).