Tyrosinase-related protein 2-derived peptide–Major Histocompatibility Complex (TRP2-MHC) (TRP2-MHC)

The Tyrosinase-related protein 2 (TRP2)-derived peptide–Major Histocompatibility Complex (MHC) is a molecular target primarily utilized in the immunotherapy of melanoma. TRP2, also known as dopachrome tautomerase (DCT), is an enzyme involved in the biosynthesis of melanin and is overexpressed in most melanoma tissues (UniProt P40126). Specific peptide fragments of TRP2, such as the HLA-A*02:01-restricted SVYDFFVWL sequence, are processed and presented on the cell surface by MHC Class I molecules (PubMed: 8691132). This presentation allows the immune system to distinguish malignant melanocytes from other cell types through T-cell receptor (TCR) recognition. Therapeutic interventions targeting this complex include peptide-based vaccines, DNA vaccines, and adoptive cell transfer using TCR-engineered T cells (PubMed: 21844380). While effective in inducing anti-tumor immunity, targeting TRP2-MHC can result in "on-target, off-tumor" toxicities because TRP2 is also expressed in healthy melanocytes located in the skin, eyes, and inner ear, potentially leading to vitiligo or uveitis (PubMed: 15155838).

Other names

DCT-derived peptide-MHCTRP-2/HLA-A*02:01 complexDopachrome tautomerase peptide-MHCTRP2-pMHCL-dopachrome tautomerase-derived peptide-MHC

Recognition of the peptide-MHC complex by specific T-cell receptors (TCRs) triggers the activation and expansion of cytotoxic T lymphocytes, which subsequently induce apoptosis in cells presenting the antigen.