Tyrosinase-related protein 2 (Dopachrome tautomerase) (TRP2)

Tyrosinase-related protein 2 (TRP2), also known as Dopachrome tautomerase (DCT), is a melanosomal enzyme essential for the biosynthesis of melanin. It catalyzes the conversion of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a critical step in the formation of eumelanin. Because TRP2 is highly expressed in melanoma cells and its expression is largely restricted to the melanocytic lineage, it is a prominent tumor-associated antigen (TAA) and a target for various cancer immunotherapies. The "P2" designation refers to a specific immunodominant peptide epitope (sequence: SVYDFFVWL) derived from the TRP2 protein, which is recognized by the immune system in the context of MHC class I molecules. Therapeutic strategies targeting TRP2 include peptide-based vaccines, DNA vaccines, and dendritic cell therapies designed to activate cytotoxic T lymphocytes (CTLs) against malignant cells. However, because TRP2 is a non-mutated self-antigen, clinical development faces challenges such as immunological tolerance and the risk of autoimmune side effects like vitiligo.

Other names

Dopachrome tautomeraseDCTTYRP2Dopachrome delta-isomeraseTRP-2L-dopachrome isomeraseMelanocyte-specific enzyme TRP2SVYDFFVWL (P2 peptide)

Induction of cytotoxic T-lymphocyte (CTL) responses via the presentation of MHC class I-restricted peptide epitopes (such as the P2 epitope SVYDFFVWL) to the T-cell receptor (TCR), leading to targeted lysis of TRP2-expressing melanoma cells.