Tyrosinase-derived peptide epitopes presented by HLA molecules (Tyrosinase-HLA complex)

Tyrosinase-derived peptide epitopes presented by HLA molecules are critical targets in the immunotherapy of melanoma (Source: PubMed, PMID: 15507677). Tyrosinase is a copper-containing enzyme essential for melanin biosynthesis, and its expression is typically restricted to melanocytes and melanoma cells (Source: UniProt, P14679). Intracellular processing of the tyrosinase protein results in short peptide fragments that are loaded onto Human Leukocyte Antigen (HLA) molecules, most commonly HLA-A*02:01, and transported to the cell surface (Source: PubMed, PMID: 8144860). These complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, making them ideal candidates for targeted therapies such as TCR-engineered T cells (TCR-T), peptide vaccines, and bispecific T-cell engagers (Source: ClinicalTrials.gov, NCT03970382). Because tyrosinase is also expressed in normal melanocytes, targeting these epitopes can lead to autoimmune-like side effects, such as vitiligo, which is often correlated with a positive therapeutic response in melanoma patients (Source: PubMed, PMID: 16322245).

Other names

Tyrosinase-MHC complexTyrosinase-derived HLA-restricted antigensMelanoma-associated antigen tyrosinase epitopesTYR-HLA-A2HLA-A*02:01-restricted tyrosinase peptides

Therapeutic agents, such as TCR-engineered T cells or bispecific engagers, bind specifically to the tyrosinase peptide-HLA complex on the tumor cell surface, triggering T-cell activation and the subsequent release of cytotoxic granules (perforin and granzymes) to induce apoptosis in the melanoma cell.