Tyrosinase peptide-HLA-A*02:01 complex (Tyrosinase/HLA-A*02:01)

The Tyrosinase peptide-HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of melanoma cells and normal melanocytes. Tyrosinase is a key enzyme in the melanin biosynthesis pathway and is highly expressed in cells of the melanocytic lineage, making it a classic lineage-specific differentiation antigen. In the context of HLA-A*02:01, the most prominent epitope is the 369-377 fragment (YMNGTMSQV), which often undergoes post-translational deamidation to YMDGTMSQV to enhance its binding and recognition by T-cells. This complex serves as a critical target for cancer immunotherapies, including T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers like ImmTACs. Because tyrosinase is also expressed in healthy melanocytes in the skin, eye, and ear, therapeutic targeting of this complex can lead to autoimmune-like side effects such as vitiligo or uveitis. Despite these risks, it remains a high-priority target due to its high prevalence and expression levels in malignant melanoma.

Other names

Tyrosinase(369-377)/HLA-A*02:01Tyr/HLA-A2 complexYMDGTMSQV-HLA-A*02:01YMNGTMSQV-HLA-A*02:01Tyrosinase-derived peptide-MHC complex

T-cell receptor (TCR) mediated recognition leading to T-cell activation and directed cytotoxicity against cells expressing the peptide-MHC complex.