HLA-A*02:01-tyrosinase (368-376, 370D) complex (HLA-A*02:01/Tyr(368-376, 370D))

The HLA-A*02:01-tyrosinase (368-376, 370D) complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target in melanoma immunotherapy (Skipper et al., 1996, J. Exp. Med.). Tyrosinase is a copper-containing enzyme essential for melanin production and is frequently overexpressed in malignant melanoma cells (UniProt P14679). The specific epitope spanning residues 368 to 376 (YMNGTMSQV) undergoes a post-translational deamidation of asparagine to aspartic acid at position 370 (YMDGTMSQV), which occurs naturally during antigen processing and significantly increases its binding stability to the HLA-A*02:01 molecule. This modified complex is recognized by the T-cell receptors (TCRs) of cytotoxic CD8+ T cells, making it a focal point for the development of TCR-engineered T-cell therapies and bispecific TCR molecules like ImmTACs. One notable therapeutic candidate targeting this complex is IMC-F10V, a bispecific protein designed to redirect T cells to kill tyrosinase-expressing melanoma cells (Immunocore). Targeting this complex allows for the selective destruction of melanoma cells, although it carries a risk of vitiligo due to the presence of tyrosinase in normal melanocytes (PubMed: 8594044). Clinical monitoring often involves assessing HLA-A*02:01 status and tyrosinase expression levels in tumor biopsies to ensure patient eligibility.

Other names

Tyrosinase 368-376 (370D) peptide-HLA-A*02:01 complexYMDGTMSQV-HLA-A*02:01HLA-A2-restricted tyrosinase epitopeModified tyrosinase 368-376 peptide

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte activation against cells presenting the specific peptide-MHC complex.