Tyrosinase-related protein 2 (TRP2)-Major Histocompatibility Complex (MHC)-restricted T-cell receptor (TCR) interface (TRP2-MHC-TCR interface)

The Tyrosinase-related protein 2 (TRP2)-Major Histocompatibility Complex (MHC)-restricted T-cell receptor (TCR) interface is a molecular complex essential for the immune recognition of melanoma cells. Tyrosinase-related protein 2, also known as dopachrome tautomerase (DCT), is an enzyme involved in the biosynthesis of melanin and is highly expressed in both normal melanocytes and malignant melanoma (UniProt P40126). In the context of this target, specific peptides derived from the TRP2 protein are processed and presented on the cell surface by MHC Class I molecules, most commonly HLA-A*02:01 (PubMed 8642301). The interface is formed when a TCR, either naturally occurring or engineered through TCR-T cell therapy, binds specifically to this peptide-MHC complex. This binding event triggers a signaling cascade within the T cell, leading to the release of cytotoxic molecules like granzymes and perforins, which induce apoptosis in the target cell (PubMed 21844331). Therapeutic strategies targeting this interface include TCR-engineered T cells and various vaccine platforms designed to expand the population of TRP2-specific cytotoxic T lymphocytes. While effective at targeting tumor cells, these therapies often face challenges related to on-target, off-tumor toxicities, such as vitiligo, due to the presence of TRP2 in healthy melanocytes.

Other names

Dopachrome tautomerase-Major Histocompatibility Complex-restricted T-cell receptor interfaceTRP-2/HLA-A*02:01 complexTRP2-MHC-TCR complexDCT-MHC-TCR interface

T-cell receptor binding to the peptide-MHC complex triggers cytotoxic T-lymphocyte activation and targeted lysis of TRP2-expressing cells.