L-dopachrome tautomerase-derived peptide-MHC class I complex (TRP-2 peptide-MHC I)

L-dopachrome tautomerase (DCT), also known as Tyrosinase-related protein 2 (TRP-2), is a 519-amino acid enzyme essential for melanin biosynthesis within the melanosomes of melanocytes (UniProt: P40126). In the context of oncology, TRP-2 is a well-characterized tumor-associated antigen (TAA) that is frequently overexpressed in melanoma cells (PubMed: 10449300). Specific peptides derived from the TRP-2 protein, such as the HLA-A*02:01-restricted epitope TRP-2:180-188 (SVYDFFVWL), are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules (PubMed: 8642306). This peptide-MHC complex serves as a primary target for various immunotherapeutic strategies, including DNA vaccines like SCIB1 and peptide-based vaccines, which aim to stimulate a CD8+ T-cell mediated immune response against the tumor (ClinicalTrials.gov: NCT01132235). Additionally, TCR-engineered T-cell therapies are being developed to specifically recognize this complex to induce tumor cell lysis. A significant therapeutic challenge is the potential for on-target, off-tumor toxicity, as TRP-2 is also expressed in normal melanocytes, often resulting in autoimmune-like side effects such as vitiligo (PubMed: 15155838).

Other names

Tyrosinase-related protein 2 peptide-MHCDCT peptide-MHCTRP-2(180-188) epitopeTRP2-MHC I complexL-dopachrome tautomerase peptide-HLA complex

Induction of antigen-specific CD8+ T-cell mediated cytotoxicity against cells presenting the TRP-2 peptide in the context of MHC class I.