Tyrosinase-related protein 2-derived peptide-MHC class I complex (TRP-2/MHC-I)

The Tyrosinase-related protein 2 (TRP-2)-derived peptide bound to MHC class I is a specific tumor-associated antigen (TAA) complex that serves as a primary target for melanoma immunotherapy (UniProt: P40126). TRP-2, also known as dopachrome tautomerase, is an enzyme involved in melanin synthesis and is highly expressed in both normal melanocytes and melanoma cells (PubMed: 8642301). Peptides derived from TRP-2, such as the immunodominant SVYDFFVWL epitope, are presented on the cell surface by MHC class I molecules, most notably HLA-A*02:01 (PubMed: 9620651). This peptide-MHC (pMHC) complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells, which triggers the release of perforins and granzymes to induce apoptosis in the target cell (PubMed: 22504444). Therapeutic interventions targeting this complex include peptide vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies designed to redirect the immune system against tumor cells (ClinicalTrials.gov: NCT00001587). A significant clinical challenge associated with targeting this complex is on-target, off-tumor toxicity, which often manifests as vitiligo due to the destruction of healthy, TRP-2-expressing melanocytes (PubMed: 15150595).

Other names

Dopachrome tautomerase peptide-MHC complexTRP-2/HLA-A*02:01 complexDCT-derived peptide-MHCTRP-2 pMHC

Recognition by cytotoxic T-cell receptors (TCRs) leading to T-cell mediated lysis of target cells.