Tyrosinase-derived peptide presented by HLA class I (TYR-HLA-I complex)

The Tyrosinase-derived peptide presented by HLA class I is a peptide-major histocompatibility complex (pMHC) that serves as a significant target for melanoma immunotherapy. Tyrosinase is a copper-containing enzyme essential for melanin biosynthesis in melanocytes, and its peptides, such as the HLA-A*02:01-restricted YMDGTMSQV, are presented on the cell surface of both normal melanocytes and melanoma cells (UniProt P14679; PMID: 7524369). Because tyrosinase is frequently overexpressed in melanoma, this pMHC complex is utilized as a tumor-associated antigen (TAA) for various therapeutic modalities, including T-cell receptor (TCR) engineered T-cells and TCR-bispecific molecules like IMC-F10V (Immuncore). These therapies are designed to recognize the specific peptide-HLA configuration, triggering a potent cytotoxic T-lymphocyte response against the tumor (PMID: 26903131). However, the expression of tyrosinase in healthy melanocytes in the skin, eye, and inner ear poses a risk of on-target, off-tumor toxicities, which can manifest as vitiligo, uveitis, or hearing impairment (PMID: 15150568). Despite these challenges, the high specificity of TCR-based recognition makes it a promising candidate for treating metastatic melanoma.

Other names

Tyrosinase-MHC complexTYR-pMHCTyrosinase-derived epitopeHLA-A*02:01-restricted tyrosinase peptideTyrosinase antigen

T-cell receptor (TCR) binding to the peptide-MHC complex leading to T-cell mediated cytotoxicity against cells expressing the antigen.