HLA-A*02:01-restricted Tyrosinase (369-377) T-cell receptor (Tyrosinase TCR)

The HLA-A*02:01-restricted Tyrosinase (369-377) T-cell receptor is a specialized antigen receptor found on CD8+ cytotoxic T cells that specifically recognizes a peptide fragment of the tyrosinase enzyme (IMDQVPFSV). Tyrosinase is a key enzyme in melanin biosynthesis and is frequently overexpressed in melanoma, making it a prominent tumor-associated antigen (TAA). The TCR recognizes this peptide only when it is presented by the specific MHC class I molecule HLA-A*02:01, a common allele in many populations. In the context of plasmacytoid dendritic cells (pDCs), this interaction can be critical for the priming and activation of the immune response, as pDCs can present tumor antigens to T cells. This TCR is a primary focus in cancer immunotherapy, particularly in the development of TCR-engineered T-cell (TCR-T) therapies. By genetically modifying a patient's T cells to express this specific TCR, clinicians can direct the immune system to selectively identify and destroy melanoma cells. While highly effective in targeting tumor cells, therapeutic use of this TCR carries risks of on-target off-tumor toxicity, such as vitiligo or uveitis, because tyrosinase is also expressed in healthy melanocytes in the skin and eyes. Clinical trials continue to evaluate the efficacy and safety of these engineered receptors in treating metastatic melanoma.

Other names

IMDQVPFSV-specific T-cell receptorTyrosinase 369-377 TCRHLA-A2-restricted Tyrosinase TCRCD8+ T-cell receptor recognizing Tyrosinase peptide 369-377

The T-cell receptor (TCR) specifically binds to the Tyrosinase-derived peptide IMDQVPFSV presented by the HLA-A*02:01 major histocompatibility complex (MHC) on the surface of target cells. This binding event triggers the formation of an immunological synapse, leading to the activation of the CD8+ T cell, secretion of cytotoxic granules (perforin and granzymes), and the subsequent lysis of the antigen-presenting tumor cell.