Human leukocyte antigen A*02:01 presenting deamidated tyrosinase peptide (N371D) (HLA-A*02:01/TYR(N371D))

The Human leukocyte antigen A*02:01 presenting deamidated tyrosinase peptide (N371D) is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical neoantigen target in melanoma immunotherapy. Tyrosinase is a copper-containing enzyme essential for melanin biosynthesis, and its expression is typically restricted to melanocytes and highly upregulated in melanoma (UniProt P14679). The specific epitope consists of the tyrosinase-derived peptide YMNGTMSQV (residues 369-377), which undergoes a critical post-translational modification where the asparagine (N) at position 371 is deamidated to aspartic acid (D) by the enzyme peptide-N-glycanase (PNGase) during cellular processing (Skipper et al., 1996, J. Exp. Med.). This deamidated peptide (YMDGTMSQV) is then loaded onto the HLA-A*02:01 molecule and presented on the cell surface for recognition by CD8+ T-cells. Therapeutic interventions targeting this complex include T-cell receptor (TCR) engineered T-cell therapies and bispecific T-cell engagers like IMC-F10V, which are designed to redirect the immune system to lyse melanoma cells (Immunocore, 2023). Clinical challenges associated with this target include "on-target, off-tumor" toxicities, as tyrosinase is also present in normal melanocytes in the skin, eyes, and inner ear. This can potentially lead to autoimmune-like reactions such as vitiligo or uveitis (Mosenson et al., 2013, J. Invest. Dermatol.). Monitoring for HLA-A*02:01 expression and tyrosinase levels is essential for patient selection in these targeted therapies.

Other names

HLA-A2/Tyrosinase(369-377) deamidated peptideYMDGTMSQV-HLA-A*02:01 complexTyrosinase 369-377 (N371D) pMHCHLA-A*02:01/TYR-D

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and cytotoxic lysis of the target cell.