Human Leukocyte Antigen A*02:01 (HLA-A*02:01) presenting tyrosinase (368-376) peptide complex (HLA-A*02:01/TYR(368-376))

The Human Leukocyte Antigen A*02:01 (HLA-A*02:01) presenting tyrosinase 368-376 peptide is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for melanoma immunotherapy. Tyrosinase is a copper-containing enzyme essential for melanin production, and its expression is largely restricted to melanocytes and melanoma cells, making it a highly specific tumor-associated antigen (TAA) [1][2]. The specific epitope, YMDGTMSQV, is a post-translationally modified version of the native sequence (YMNGTMSQV), where an asparagine is deamidated to aspartic acid, a process essential for its recognition by the immune system [3]. This complex is presented on the cell surface by the HLA-A*02:01 allele, which is prevalent in approximately 40-50% of the Caucasian population [4]. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T cells and bispecific T-cell engagers (such as ImmTACs), which are designed to recognize the pMHC with high affinity and trigger a cytotoxic immune response against the tumor [5][6]. While effective in targeting melanoma, these therapies carry risks of on-target off-tumor toxicities, such as vitiligo or ocular inflammation, due to the presence of tyrosinase in healthy melanocytes [7].

Other names

HLA-A*02:01-YMDGTMSQVTyrosinase 368-376 peptide-HLA-A*02:01 complexHLA-A2-Tyr368Tyrosinase(369-377)HLA-A*02:01 presenting deamidated tyrosinase peptide

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