Programmed death-ligand 1-derived peptide–Major Histocompatibility Complex (PD-L1-pMHC)

The Programmed death-ligand 1 (PD-L1)-derived peptide–Major Histocompatibility Complex (MHC) is a specialized immunological target formed when intracellularly processed fragments of the PD-L1 protein are presented on the cell surface by MHC molecules, most commonly HLA-A*02:01. While PD-L1 is widely known as an immune checkpoint ligand that suppresses T-cell activity through the PD-1 receptor, it also serves as a source of endogenous antigens that can be recognized by the immune system. These PD-L1-derived peptides are presented by both tumor cells and immunosuppressive cells within the tumor microenvironment, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells. Specific T-cell receptors (TCRs) on cytotoxic T lymphocytes can recognize these pMHC complexes, triggering the destruction of the presenting cells. Therapeutic strategies targeting this complex include peptide vaccines like IO-103, which stimulate the expansion of natural PD-L1-specific T cells, as well as engineered TCR-T cell therapies and TCR-like antibodies (TCR-mimetics). By targeting the pMHC complex rather than the whole protein, these therapies aim to selectively eliminate cells that utilize the PD-L1 pathway to evade immune surveillance.

Other names

PD-L1 peptide-HLA complexPD-L1/HLA-A*02:01 complexHLA-presented PD-L1 peptidePD-L1 pMHCPD-L1 epitope-MHC complex

T-cell mediated cytotoxicity and targeted cell lysis via T-cell receptor (TCR) recognition of the peptide-MHC complex.