Tyrosinase peptide–Human leukocyte antigen A*0201 complex (Tyr-HLA-A*0201)

The Tyrosinase peptide–Human leukocyte antigen A*0201 complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of cells, including dendritic cells and melanoma cells. Tyrosinase is a copper-containing enzyme essential for melanin production and is considered a lineage-specific tumor-associated antigen due to its high expression in melanoma (UniProt P14679; Brichard et al., 1993, J Exp Med). The complex is formed when the HLA-A*0201 molecule, a common Class I MHC allele, binds a specific immunodominant peptide derived from tyrosinase, most notably the 369-377 fragment (YMDGTMSQV) (Wolfel et al., 1994, Eur J Immunol). This complex is a primary target for the immune system, as it is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering their activation and subsequent lysis of target cells (PubMed 8144862). In clinical applications, dendritic cells are often pulsed with these peptides or engineered to express them to serve as potent vaccines that prime and expand tyrosinase-specific T cells in patients (Banchereau & Palucka, 2005, Nat Rev Immunol). While this strategy shows promise for treating metastatic melanoma, therapeutic challenges include the potential for vitiligo, an autoimmune condition resulting from the destruction of healthy melanocytes that also express tyrosinase.

Other names

Tyrosinase(369-377)-HLA-A*0201 complexpMHC complex (Tyrosinase/HLA-A*0201)Tyrosinase-derived peptide-MHC class I complexYMDGTMSQV-HLA-A*0201 complex

The complex acts as a specific ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes. When presented by dendritic cells, it facilitates the priming and expansion of naive T cells; when presented on the surface of melanoma cells, it serves as a recognition signal for activated T cells to induce pore formation and apoptosis in the tumor cell.