HLA-A*02:01-tyrosinase peptide complex (HLA-A*02:01/Tyr)

The HLA-A*02:01-tyrosinase peptide complex is a specific antigen-presenting structure formed by the association of the Human Leukocyte Antigen (HLA) allele A*02:01 and a peptide fragment derived from the tyrosinase enzyme (UniProt P01892; UniProt P14679). Tyrosinase is a copper-containing enzyme essential for melanin production and is highly expressed in melanocytes and melanoma cells, making it a prominent tumor-associated antigen (TAA). In patients carrying the HLA-A*02:01 allele, the immune system can recognize the tyrosinase-derived peptide, commonly the 369-377 sequence YMDGTMSQV, when it is presented on the cell surface within the MHC class I groove (PMID: 8145037). This complex is a primary target for cancer immunotherapies, including T-cell receptor (TCR) engineered T-cells and bispecific molecules like ImmTACs, which are designed to redirect T-cells to kill melanoma cells. While this target offers high specificity for melanocytic lineage cells, its presence in normal melanocytes can lead to on-target, off-tumor toxicities such as vitiligo or ocular inflammation. Consequently, it remains a significant focus for developing precision treatments for metastatic melanoma.

Other names

HLA-A2/TyrosinaseTyrosinase 369-377 peptide-HLA-A*02:01 complexMHC-peptide complex (HLA-A*02:01/Tyr)pMHC (HLA-A*02:01/YMDGTMSQV)

Recognition by T-cell receptors (TCRs) or TCR-like molecules leading to cytotoxic T-lymphocyte activation and lysis of target cells.