Tyrosinase-related protein 2 peptide-MHC-restricted T-cell receptor (TRP-2 TCR)

The Tyrosinase-related protein 2 (TRP-2) peptide-MHC-restricted T-cell receptor is a specialized immune receptor designed to recognize specific fragments of the TRP-2 protein presented by Major Histocompatibility Complex (MHC) molecules on the surface of cells. TRP-2, also known as dopachrome tautomerase (DCT), is an enzyme essential for melanin biosynthesis and is frequently overexpressed in melanoma, making it a significant target for cancer immunotherapy (UniProt P40126). T-cell receptors (TCRs) specific for TRP-2 allow the immune system to distinguish malignant melanocytes from other cell types, although they may also target healthy melanocytes (PubMed: 10508250). In clinical applications, patient T cells are often engineered to express these TCRs (TCR-T therapy) to treat advanced melanoma by inducing direct cytotoxic activity against tumor cells (PubMed: 21844595). While effective in promoting tumor regression, this approach carries risks of autoimmune reactions, such as vitiligo or uveitis, due to the presence of TRP-2 in normal pigmented tissues (PubMed: 15155838). This receptor complex is a cornerstone of personalized adoptive cell transfer strategies aiming to provide long-term anti-tumor immunity.

Other names

TRP-2-specific T-cell receptorDCT-specific TCRDopachrome tautomerase-specific T-cell receptorTRP-2/HLA-A2 restricted TCRTyrosinase-related protein 2-restricted T-cell receptor

The TRP-2 TCR-engineered T-cells recognize and bind to the TRP-2 peptide presented by MHC molecules (typically HLA-A*02:01) on melanoma cells, triggering T-cell activation and subsequent lysis of the target tumor cells (PubMed: 21844595).