Tyrosinase peptide–HLA-A*0201 complex (Tyrosinase/HLA-A*0201)

The Tyrosinase peptide–HLA-A*0201 complex is a specific antigenic target presented on the surface of cells, primarily melanocytes and melanoma cells (Source: PubMed PMID: 8140443). It consists of a processed peptide fragment derived from the tyrosinase enzyme, typically the 369-377 sequence (YMDGTMSQV), bound within the groove of the Human Leukocyte Antigen (HLA) A*0201 molecule (Source: PubMed PMID: 15150570). Tyrosinase is a key enzyme in melanin biosynthesis and is frequently overexpressed in malignant melanoma, making this complex a highly specific marker for the disease (Source: PubMed PMID: 21148331). In the context of immunotherapy, this complex serves as a target for T-cell receptors (TCRs) on cytotoxic T lymphocytes. Therapeutic strategies include the development of TCR-engineered T cells (TCR-T) and bispecific T-cell engagers, such as ImmTACs (e.g., IMC-F10V), which redirect the immune system to recognize and destroy cells displaying this specific peptide-MHC signature (Source: Immunocore). However, because tyrosinase is also expressed in normal melanocytes, targeting this complex can lead to autoimmune-like side effects such as vitiligo or ocular inflammation (Source: PubMed PMID: 10449300).

Other names

Tyrosinase(369-377)/HLA-A*02:01Tyr-HLA-A2 complexTyrosinase-MHC class I complexYMDGTMSQV-HLA-A*02:01Tyrosinase-derived peptide-MHC complex

The complex acts as a ligand for specific T-cell receptors (TCRs). Therapeutic agents like TCR-engineered T cells or bispecific TCR molecules (ImmTACs) bind to this peptide-MHC complex on the surface of melanoma cells, triggering T-cell mediated lysis of the tumor cell (Source: PubMed PMID: 21148331).