HLA-A*02:01-restricted tyrosinase (368-376) epitope (HLA-A2/Tyr368-376)

The HLA-A*02:01-presented tyrosinase 368-376 epitope is a prominent tumor-associated antigen (TAA) utilized in the development of immunotherapies for melanoma. Tyrosinase is a copper-containing enzyme essential for melanin biosynthesis, and its expression is highly restricted to melanocytes and their malignant counterparts. The specific epitope consists of a nine-amino acid peptide (originally YMNGTMSQV, often post-translationally deamidated to YMDGTMSQV) presented by the Class I Human Leukocyte Antigen (HLA) allele A*02:01. This peptide-MHC complex is recognized by specific T-cell receptors (TCRs), making it a viable target for TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers like ImmTACs. Because tyrosinase is also expressed in healthy melanocytes, therapeutic targeting can lead to on-target, off-tumor toxicities such as vitiligo or ocular inflammation. Despite these challenges, it remains a key target in precision oncology due to its high prevalence in HLA-A2 positive melanoma patients.

Other names

Tyrosinase peptide 368-376YMNGTMSQVYMDGTMSQVHLA-A*02:01/Tyrosinase(368-376)Tyrosinase(368-376) peptide-MHC complex

Recognition of the peptide-MHC complex by engineered T-cell receptors (TCRs) or bispecific molecules to induce T-cell mediated lysis of tumor cells.