T-cell receptor recognizing Tyrosinase-related protein 2 (TRP2) peptide-MHC complex (TRP2-specific TCR)

The T-cell receptor (TCR) recognizing Tyrosinase-related protein 2 (TRP2) peptide-MHC complexes is a specialized immune receptor engineered for use in adoptive cell transfer therapies, particularly for treating melanoma. TRP2, also known as dopachrome tautomerase (DCT), is a melanocyte-specific enzyme involved in melanin biosynthesis that is frequently overexpressed in melanoma cells [UniProt P40126]. The TCR is designed to specifically bind to a TRP2-derived peptide, such as the P30 epitope (SVYDFFVWL), when it is presented on the cell surface by Major Histocompatibility Complex (MHC) molecules like HLA-A*02:01 or H-2Kb [PubMed 9151715]. Upon recognition of this antigen-MHC complex, the TCR initiates a signaling cascade within the T cell, leading to the secretion of cytotoxic molecules like granzymes and perforins, as well as pro-inflammatory cytokines like IFN-gamma, which collectively induce apoptosis in the tumor cell [PubMed 21149614]. Because TRP2 is also expressed in normal melanocytes, therapeutic application of this TCR can lead to on-target, off-tumor toxicities, most commonly manifesting as vitiligo or pigment loss in the skin and eyes [PubMed 15155838]. Current research focuses on optimizing TCR affinity to maximize anti-tumor efficacy while minimizing these autoimmune side effects.

Other names

TRP-2-specific T-cell receptorDopachrome tautomerase-specific TCRTRP2/P30-specific TCRDCT-specific TCR

Recognition of TRP2 peptide-MHC complexes on the surface of tumor cells, triggering T-cell activation and subsequent lysis of the target cell.