Tyrosinase-derived melanoma-associated peptide epitopes presented by HLA-A*0201 (Tyrosinase/HLA-A*02:01 complex)

Tyrosinase-derived melanoma-associated peptide epitopes presented by HLA-A*0201 are critical targets in the development of immunotherapies for malignant melanoma. Tyrosinase is a copper-containing enzyme essential for melanin production, and its expression is largely restricted to melanocytes and melanoma cells, making it a classic tumor-associated antigen (TAA) (UniProt P14679). In HLA-A*02:01-positive patients, specific tyrosinase-derived peptides, most notably the 369-377 (YMDGTMSQV) and 1-9 (MLLAVLYCL) sequences, are processed and displayed on the cell surface within the MHC Class I groove (PMID: 8144860). These peptide-MHC (pMHC) complexes are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, which then initiate the destruction of the target cell through the release of perforins and granzymes (PMID: 8345261). Interestingly, the 369-377 epitope often undergoes post-translational deamidation (Asn to Asp) to enhance its binding and recognition (PMID: 9743335). Therapeutic interventions leveraging this target include peptide vaccines designed to expand endogenous T-cell populations and adoptive cell therapies using TCR-engineered T cells (TCR-T) (NCT02395692). However, because tyrosinase is also present in healthy melanocytes in the skin and eyes, treatment can lead to autoimmune-like side effects such as vitiligo and uveitis (PMID: 19860757).

Other names

Tyrosinase peptide-HLA-A2 complexHLA-A*02:01-restricted tyrosinase epitopesTyrosinase (369-377) peptideTyrosinase (1-9) peptideTyr/HLA-A2YMDGTMSQV/HLA-A*02:01MLLAVLYCL/HLA-A*02:01

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) on CD8+ T cells, triggering cytotoxic immune responses against cells expressing the antigen.