T-cell receptor specific for programmed cell death 1 ligand 2-derived peptide-HLA complexes (PD-L2-specific TCR)

T-cell receptors (TCRs) specific for PD-L2–derived peptide–HLA complexes are specialized immune receptors that recognize fragments of the Programmed Death-Ligand 2 (PD-L2) protein presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Source: PMID: 24608583). While PD-L2 typically functions as an immune checkpoint ligand that suppresses T-cell activity by binding to PD-1, these specific TCRs allow cytotoxic T cells to identify and eliminate cells expressing high levels of PD-L2 (Source: IO Biotech). This targeting strategy is particularly relevant in oncology, as many tumors and immunosuppressive myeloid cells upregulate PD-L2 to evade the immune system. By engaging these TCRs—either through peptide vaccines like IO102 or adoptive cell therapies—the immune system can directly deplete the immunosuppressive components of the tumor microenvironment (Source: Nature Communications 2014, 5:3433). This dual action of killing tumor cells and removing pro-tumor immune cells enhances the overall anti-tumor response and can synergize with standard checkpoint inhibitors like pembrolizumab (Source: ClinicalTrials.gov NCT03562871).

Other names

PD-L2-specific T-cell receptorTCR specific for PD-L2 peptide-MHCAnti-PD-L2 TCRPDCD1LG2-specific T-cell receptor

Recognition of PD-L2-derived peptides presented by HLA molecules on the surface of tumor cells or immunosuppressive immune cells, leading to T-cell activation and direct lysis of the target cells.