Tyrosinase-derived peptide-HLA-A*02:01 complex (TYR/HLA-A*02:01)

The Tyrosinase-derived peptide-HLA-A*02:01 complex is a specific immunological target formed by the presentation of intracellularly processed tyrosinase fragments on the surface of cells via the Major Histocompatibility Complex (MHC) class I molecule HLA-A*02:01. Tyrosinase is a rate-limiting enzyme in melanin biosynthesis, and while it is expressed in normal melanocytes, it is significantly overexpressed in the majority of malignant melanomas (Wolfel et al., 1994, Eur. J. Immunol.). The most prominent peptide associated with this complex is the 9-amino acid sequence YMDGTMSQV (residues 369-377), which is recognized by the T-cell receptors (TCRs) of cytotoxic CD8+ T cells (Skipper et al., 1996, J. Exp. Med.). This specific peptide often undergoes a post-translational deamidation of an asparagine to aspartic acid to enhance its binding affinity and immunogenicity. Therapeutic strategies targeting this complex include TCR-engineered T cells (TCR-T), bispecific T-cell engagers like IMC-F10V, and peptide-based vaccines designed to stimulate an endogenous anti-tumor immune response (Hassane et al., 2016, J. Immunother. Cancer). A significant clinical challenge in targeting this complex is the potential for on-target, off-tumor toxicity, as tyrosinase is also present in healthy melanocytes in the skin, eyes, and inner ear, potentially leading to vitiligo or inflammatory conditions like uveitis (Yee et al., 2000, J. Exp. Med.).

Other names

HLA-A*02:01-restricted tyrosinase antigenTYR:369-377/HLA-A*02:01TYR:1-9/HLA-A*02:01Tyrosinase-MHC class I complexYMDGTMSQV/HLA-A*02:01

T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity against cells presenting the tyrosinase peptide