Programmed death-ligand 1 peptide-major histocompatibility complex (PD-L1-pMHC) (PD-L1-pMHC)

The Programmed death-ligand 1 (PD-L1) peptide presented in the Major Histocompatibility Complex (MHC) is a specialized immunological target consisting of intracellularly processed PD-L1 fragments displayed on the cell surface (He et al., 2021, Journal of Hematology & Oncology). While conventional PD-L1 therapies target the full-length surface protein to disrupt the PD-1/PD-L1 inhibitory axis, the PD-L1-pMHC complex serves as a direct marker for T-cell recognition (Liu et al., 2017, Nature Communications). This target is particularly relevant in oncology, where tumor cells frequently overexpress PD-L1 as a mechanism of immune evasion. By utilizing T-cell receptor (TCR)-engineered T-cells or TCR-like antibodies (TCRm), clinicians can direct a potent cytotoxic response specifically against cells presenting these PD-L1-derived epitopes (Eureka Therapeutics, 2023). This approach offers a potential advantage in treating cold tumors or those resistant to standard checkpoint inhibitors by converting the immunosuppressive PD-L1 molecule into a target for destruction. Clinical applications often focus on specific HLA-restricted peptides, such as the HLA-A*02:01-restricted PD-L1_15-23 epitope (PubMed, PMID: 28533445).

Other names

PD-L1 peptide-MHC complexHLA-presented PD-L1 peptidePD-L1-derived epitopePD-L1/HLA complexCD274 peptide-MHC

Targeting of the peptide-MHC complex by engineered T-cells or antibodies to induce direct lysis of PD-L1-expressing tumor cells.