HLA-A*02:01-restricted tyrosinase (368–376) peptide-MHC complex (HLA-A*02:01/Tyr368-376)

The HLA-A*02:01-restricted tyrosinase (368–376) peptide-MHC complex is a highly specific immunotherapy target primarily expressed on the surface of melanoma cells and normal melanocytes (Skipper et al., 1996, J Exp Med). Tyrosinase is the rate-limiting enzyme in melanin biosynthesis, and its 368–376 epitope (sequence YMDGTMSQV) is generated through post-translational deamidation before being presented by the HLA-A*02:01 molecule (Mosse et al., 1998, J Exp Med). This complex serves as a recognition site for T-cell receptors (TCRs), making it a focal point for the development of TCR-engineered T-cell therapies and bispecific T-cell engagers like IMC-F10V (Immunocore, 2023). Because tyrosinase expression is largely confined to the melanocytic lineage, it offers a relatively narrow expression profile, though on-target, off-tumor effects can occur in healthy tissues containing melanocytes, such as the skin, retina, and inner ear (Yee et al., 2000, J Exp Med). Clinical applications focus on treating metastatic melanoma in patients who carry the HLA-A*02:01 allele, utilizing the immune system's ability to detect these specific peptide-MHC signatures to induce tumor cell lysis.

Other names

Tyrosinase 368-376 peptideYMNGTMSQVYMDGTMSQVHLA-A2 tyrosinase peptideTyrosinase(368-376) HLA-A*02:01 complexMelanoma-associated antigen tyrosinase

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation, secretion of cytotoxic granules (perforin/granzyme), and targeted lysis of melanoma cells.