Tyrosinase-related protein 2 (180-188)-specific T-cell receptor (TRP-2 TCR)

The TRP-2:180-188–specific T-cell receptor is a specialized protein complex expressed on CD8+ cytotoxic T lymphocytes that recognizes the SVYDFFVWL peptide derived from Tyrosinase-related protein 2 (TRP-2), also known as Dopachrome tautomerase (DCT) [PMID: 10754337]. TRP-2 is a melanocyte differentiation antigen frequently overexpressed in melanoma, making it a key target for adoptive T-cell therapies [PMID: 15150595]. This TCR specifically binds the peptide when presented by the HLA-A*02:01 molecule, initiating a signaling cascade that results in the targeted destruction of tumor cells [PMID: 21760633]. In clinical settings, patients' T cells are genetically modified to express this TCR to enhance the anti-tumor immune response against metastatic melanoma [PMID: 24030377]. However, because TRP-2 is also expressed in normal melanocytes in the skin and eyes, therapy can lead to on-target, off-tumor toxicities such as vitiligo and uveitis [PMID: 18413825]. Monitoring for these autoimmune-like reactions and cytokine release syndrome is essential for patient safety during treatment.

Other names

Dopachrome tautomerase-specific T-cell receptorTRP-2:180-188 TCRSVYDFFVWL-specific T-cell receptorTRP2-specific TCR

The TCR specifically recognizes the SVYDFFVWL peptide (amino acids 180-188) of Tyrosinase-related protein 2 presented by the HLA-A*02:01 major histocompatibility complex, triggering T-cell activation, cytokine production, and granzyme-mediated lysis of melanoma cells [PMID: 10754337, 21760633].