Tyrosinase-related protein 2 peptide–MHC class I complex (TRP2-pMHC)

Tyrosinase-related protein 2 (TRP2), also known as dopachrome tautomerase (DCT), is a melanocyte-specific enzyme and a well-characterized melanoma-associated antigen (TAA) [1][2]. The TRP2 peptide–MHC class I complex consists of a TRP2-derived peptide (e.g., the HLA-A*02:01-restricted SVYDFFVWL) presented on the cell surface within the Major Histocompatibility Complex [2][3]. This complex is the specific target for TRP2-specific T cell receptors (TCRs) found on cytotoxic CD8+ T cells [3][4]. When a TCR engages this pMHC complex, it triggers T cell activation, leading to the secretion of cytotoxic granules and the destruction of the target melanoma cell [4][5]. Therapeutic approaches targeting this interaction include TCR-engineered T cell (TCR-T) therapies and cancer vaccines designed to enhance the immune system's ability to recognize TRP2-expressing tumors [5][6]. However, because TRP2 is also expressed in normal melanocytes, these therapies carry a risk of on-target, off-tumor toxicities, such as vitiligo and uveitis [1][6].

Other names

DCT peptide-MHC complexTRP-2/HLA-A*02:01 complexTRP-2/H-2Kb complexDopachrome tautomerase peptide-MHC complexTRP2-specific TCR target

The TRP2-pMHC complex acts as a ligand for TRP2-specific T cell receptors (TCRs); their engagement triggers cytotoxic T lymphocyte activation and targeted lysis of TRP2-expressing cells.