Tyrosinase-specific T-cell receptor (Tyrosinase-TCR)

The tyrosinase-specific T-cell receptor (TCR) is a specialized protein complex found on the surface of CD8+ T cells that specifically recognizes tyrosinase-derived peptides presented by HLA class I molecules, most commonly HLA-A*02:01 (Robbins et al., 2011). Tyrosinase is a melanocyte differentiation antigen that is highly expressed in melanoma cells, making it a prime target for cancer immunotherapy (UniProt P14679). By engineering T cells to express these specific TCR clonotypes, clinicians can direct the patient's immune system to selectively identify and eliminate malignant melanoma cells (Morgan et al., 2006). This approach, known as TCR-T cell therapy, leverages the high specificity of the TCR for intracellular antigens that are processed and presented on the cell surface. However, because tyrosinase is also expressed in normal melanocytes, therapeutic interventions can lead to autoimmune-like side effects such as vitiligo, uveitis, or hearing loss (Yee et al., 2000). Ongoing research focuses on optimizing TCR affinity and improving the persistence of these engineered cells within the tumor microenvironment to enhance clinical outcomes (NCT02366546).

Other names

Antigen-specific T-cell receptor clonotypes on CD8+ T cells recognizing tyrosinase peptide–HLA class I complexesTyrosinase-reactive T-cell receptorHLA-A*02:01-restricted tyrosinase TCRAnti-tyrosinase TCRTyrosinase 369-377 TCR

Adoptive transfer of T cells genetically engineered to express a high-affinity TCR specific for the tyrosinase 369-377 peptide presented by HLA-A*02:01, leading to MHC-restricted recognition and targeted destruction of tyrosinase-expressing melanoma cells.