Tyrosinase-derived melanoma antigen peptide–Major Histocompatibility Complex (Tyr-MHC)

The Tyrosinase-derived melanoma antigen peptide–MHC complex is a cell-surface antigen composed of a specific peptide fragment from the tyrosinase enzyme bound to a Major Histocompatibility Complex (MHC) molecule, typically HLA-A*02:01 (PMID: 8389191). Tyrosinase is a copper-containing enzyme essential for melanin production and is considered a melanocyte-differentiation antigen that is overexpressed in the majority of malignant melanomas (PMID: 7513014). This peptide-MHC (pMHC) complex serves as a ligand for T-cell receptors (TCRs) on CD8+ cytotoxic T cells, facilitating the immune system's ability to identify and destroy melanocytes and melanoma cells (PMID: 15585850). Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies and bispecific T-cell engagers, such as ImmTAC molecules like IMC-F10V, which aim to enhance the anti-tumor immune response (PMID: 30104351). However, because tyrosinase is also expressed in healthy melanocytes, targeting this complex can lead to on-target, off-tumor toxicities, including vitiligo, uveitis, and hearing loss (PMID: 21931025).

Other names

Tyrosinase-HLA-A*02:01 complexTyr-pMHCTyrosinase-derived peptide-MHC complexHLA-A2-restricted tyrosinase antigenTyrosinase 369-377 peptide-HLA complex

T-cell receptor (TCR) mediated recognition leading to T-cell redirection, activation, and cytotoxic lysis of target cells.