T-cell receptor specific for Tyrosinase-related protein 2 (TRP-2) peptide-MHC class I complex (TRP-2-specific TCR)

The T-cell receptor (TCR) specific for Tyrosinase-related protein 2 (TRP-2) peptide presented by MHC class I is a critical component in the cellular immune response against melanoma (PubMed: 10449771). TRP-2, also known as dopachrome tautomerase (DCT), is a melanocyte-differentiation antigen that is highly expressed in both normal melanocytes and melanoma cells (UniProt: P40126). When these specific TCRs, either naturally occurring or engineered into T cells (TCR-T therapy), bind to the TRP-2/MHC-I complex, they initiate a signaling cascade that leads to the activation of CD8+ cytotoxic T lymphocytes (PubMed: 21844364). This activation results in the targeted destruction of cells expressing the TRP-2 antigen through the release of perforins and granzymes. Because TRP-2 is a self-antigen, therapeutic strategies targeting this receptor must balance anti-tumor efficacy with the risk of autoimmunity, such as vitiligo or ocular inflammation, caused by the destruction of healthy melanocytes (PubMed: 15155838).

Other names

TRP-2/MHC-I specific TCRDopachrome tautomerase-specific T-cell receptorDCT-specific TCRTRP-2-specific T-cell receptor

The mechanism involves the specific binding of the TCR to the TRP-2 peptide (often residues 180-188) presented by HLA-A*02:01, which triggers the CD3 signaling complex and leads to the release of cytotoxic granules (PubMed: 21844364).