HLA-A*02:01-tyrosinase (368-376) peptide complex (HLA-A*02:01-Tyr(368-376))

The HLA-A*02:01-tyrosinase (368-376) peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a prominent target for melanoma immunotherapy. It comprises a 9-amino acid epitope, YMDGTMSQV, derived from the tyrosinase enzyme—a key protein in melanin synthesis—presented by the HLA-A*02:01 allele [PMID: 7524369]. This complex is highly expressed on the surface of melanoma cells, making it a viable target for T-cell receptor (TCR)-based therapies, including TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers like ImmTACs (e.g., IMC-F10V) [Immuncore]. These therapeutic agents are engineered to bind the pMHC complex with high affinity, redirecting T-cells to recognize and eliminate tumor cells. While effective, the expression of tyrosinase in normal melanocytes can lead to on-target, off-tumor toxicities, most commonly manifesting as vitiligo, but potentially affecting the eyes and inner ear [PMID: 15150594]. Consequently, patient selection requires HLA-A*02:01 genotyping and confirmation of tyrosinase expression in the tumor.

Other names

HLA-A*02:01-YMDGTMSQVTyrosinase 368-376/HLA-A*02:01 complexTyr368-376/A2YMDGTMSQV/HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to the formation of an immunological synapse, T-cell activation, and the release of cytotoxic granules (perforin and granzymes) to induce apoptosis in the target cell [PMID: 25108347].