Human leukocyte antigen A*02:01–Tyrosinase peptide complex (HLA-A2–Tyrosinase)

The HLA-A2–Tyrosinase peptide complex is a specific peptide-major histocompatibility complex (pMHC) consisting of the HLA-A*02:01 molecule presenting a 9-amino acid fragment derived from the tyrosinase enzyme, typically the TYR(369–377) sequence (YMDGTMSQV). Tyrosinase is a key enzyme in melanin biosynthesis and is highly overexpressed in most melanoma cells, making this complex a prominent tumor-associated antigen. Because HLA-A2 is one of the most common MHC alleles in the Caucasian population, this complex serves as a critical target for precision immunotherapy. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cell therapies and bispecific T-cell engagers, such as ImmTACs (Immune mobilizing monoclonal TCRs against cancer). These drugs are designed to recognize the specific pMHC on the surface of malignant cells and trigger a potent cytotoxic immune response. However, because tyrosinase is also expressed in healthy melanocytes, clinical challenges include managing on-target off-tumor toxicities such as vitiligo or ocular inflammation. Monitoring HLA-A2 status and tyrosinase expression levels is essential for patient selection in clinical trials.

Other names

HLA-A*02:01/TYR(369-377)HLA-A2/Tyrosinase(369-377) complexpMHC complex (HLA-A2/Tyrosinase)Tyrosinase-derived peptide-MHC complex

Targeting by T-cell receptor (TCR) mimics or engineered TCRs to induce T-cell mediated lysis of tumor cells presenting the tyrosinase peptide.