T-cell receptor recognizing PD-L1 peptide–HLA complex (PD-L1 TCR)

T-cell receptors (TCRs) recognizing PD-L1 peptide–HLA complexes are specialized immune receptors that enable T cells to identify and eliminate cells expressing the programmed death-ligand 1 (PD-L1) protein (Munir et al., 2013; Jørgensen et al., 2020). While PD-L1 typically functions as an immune checkpoint ligand that inhibits T-cell activity through the PD-1 receptor, it can also be processed into intracellular peptides and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Frontiers in Immunology, 2020). T cells equipped with these specific TCRs can recognize these peptide-HLA complexes, effectively turning a molecule used for immune evasion into a target for immune attack (MDPI, 2021). This mechanism is leveraged in cancer immunotherapy to target both PD-L1-expressing tumor cells and immunosuppressive cells within the tumor microenvironment, such as regulatory T cells and myeloid-derived suppressor cells (IO Biotech, 2024). Therapeutic approaches include the use of peptide vaccines, such as IO103, which stimulate the expansion of endogenous PD-L1-specific T cells, as well as the development of adoptive TCR-engineered T-cell (TCR-T) therapies (ClinicalTrials.gov, NCT03042793). By activating these T cells, clinicians aim to overcome the immunosuppressive barriers of the tumor and enhance the efficacy of other treatments like checkpoint inhibitors (NIH, 2025). However, because PD-L1 is also expressed on some healthy tissues, such as vascular endothelium and activated immune cells, therapies targeting these TCR-peptide-HLA interactions must be carefully managed to avoid off-tumor toxicity and autoimmune reactions (Springer Medizin, 2025).

Other names

PD-L1-specific T-cell receptorAnti-PD-L1 TCRT-cell receptor targeting PD-L1/MHC complexesPD-L1-reactive T-cell receptor

Recognition of PD-L1-derived peptides (such as those from the signal sequence) presented on HLA class I molecules (e.g., HLA-A*02:01) by specific T-cell receptors, which triggers T-cell activation and the subsequent lysis of PD-L1-expressing tumor and immunosuppressive cells.