Tyrosinase-related protein 2-derived peptide presented by Major Histocompatibility Complex class I (TRP-2/MHC-I)

Tyrosinase-related protein 2 (TRP-2), also known as dopachrome tautomerase (DCT), is a key enzyme in the melanin biosynthetic pathway (UniProt P40126). Peptides derived from TRP-2, such as the HLA-A*02:01-restricted SVYDFFVWL, are processed and presented by Major Histocompatibility Complex (MHC) class I molecules on the surface of melanocytes and melanoma cells (PubMed: 8885111). This peptide-MHC complex serves as a critical target for cancer immunotherapy because TRP-2 is highly expressed in most human melanoma samples (PubMed: 10623514). Therapeutic approaches targeting this complex include peptide vaccines, DNA vaccines, and TCR-engineered T-cell therapies designed to induce a cytotoxic T-lymphocyte (CTL) response (PubMed: 21149615). Recognition of the TRP-2/MHC-I complex by the T-cell receptor (TCR) triggers the release of cytotoxic granules, leading to the destruction of the presenting cell. While effective in targeting tumor cells, these therapies often face the challenge of on-target, off-tumor toxicity. Because TRP-2 is also present in healthy melanocytes in the skin and eyes, treatment can potentially lead to autoimmune conditions such as vitiligo or uveitis (PubMed: 15155838). Clinical monitoring often involves assessing HLA-A*02:01 status and TRP-2 expression levels in tumor biopsies to ensure target availability.

Other names

Dopachrome tautomerase-derived peptide/MHC complexTRP-2 peptide-HLA complexDCT-derived peptide presented by MHC class ITRP-2/HLA-A*02:01 complex

Therapeutic agents target this complex to activate or provide CD8+ cytotoxic T-lymphocytes that recognize the specific TRP-2 peptide sequence in the context of MHC class I, leading to the targeted lysis of melanoma cells.