Tyrosinase-related protein 2 (TRP-2) (TRP-2)

Tyrosinase-related protein 2 (TRP-2), also known as dopachrome tautomerase (DCT), is a membrane-bound enzyme located in the melanosomes of melanocytes, where it catalyzes the conversion of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) during melanin synthesis (UniProt: P40126). In the context of oncology, TRP-2 is a prominent tumor-associated antigen (TAA) because it is highly and consistently expressed in melanoma cells across various stages of the disease (Wang et al., 1996, PubMed: 8691132). The MHC class I-restricted epitopes of TRP-2, such as the HLA-A*02:01-binding peptide SVYDFFVWL (TRP-2 180-188), are critical targets for immunotherapy as they allow the immune system to recognize and destroy malignant melanocytes (Parkhurst et al., 1998, PubMed: 9743341). Therapeutic interventions, including DNA vaccines like SCIB1 and various peptide-based or dendritic cell vaccines, aim to activate cytotoxic T lymphocytes (CTLs) to recognize these specific MHC-peptide complexes on the surface of tumor cells (Scancell, 2023; ClinicalTrials.gov: NCT01138013). A significant challenge in targeting TRP-2 is its status as a self-antigen, which can lead to immune tolerance or on-target, off-tumor toxicity, typically manifesting as vitiligo due to the destruction of healthy pigment-producing cells (Bowne et al., 1999, PubMed: 10449300).

Other names

Dopachrome tautomeraseDCTTRP2L-dopachrome Delta-isomeraseL-dopachrome tautomerase

Induction of antigen-specific cytotoxic T lymphocyte (CTL) responses against MHC class I-restricted TRP-2 epitopes on tumor cells.