Tyrosinase-related protein 2-derived peptide–Major Histocompatibility Complex class I complex (TRP2-pMHC I)

The Tyrosinase-related protein 2 (TRP2)-derived peptide–Major Histocompatibility Complex (MHC) class I complex is a key immunological target in melanoma immunotherapy (Wang et al., 1996, PMID: 8691132). TRP2, also known as dopachrome tautomerase (DCT), is an enzyme in the melanin synthesis pathway that is highly expressed in melanoma cells and normal melanocytes (Parkhurst et al., 1998, PMID: 9433301). Specific TRP2 peptides, most notably the TRP2:180-188 epitope (SVYDFFVWL), are processed and presented on the cell surface by MHC class I molecules, such as HLA-A*02:01 in humans, to CD8+ T cells (Bloom et al., 1997, PMID: 9236105). This recognition triggers a cytotoxic immune response against the tumor cells. Clinical approaches include peptide vaccines and T-cell receptor (TCR)-engineered T-cell therapies (TCR-T) designed to recognize this specific pMHC complex (Singh et al., 2014, PMID: 25103354). However, because TRP2 is also expressed in healthy melanocytes, targeting this complex can lead to autoimmune side effects such as vitiligo or uveitis (Overwijk et al., 1999, PMID: 10426935).

Other names

TRP-2 peptide-MHC complexDopachrome tautomerase peptide-MHC complexTRP2/HLA-A*02:01 complexDCT-derived peptide-MHC complexTRP2(180-188)/HLA-A2 complex

Activation of antigen-specific CD8+ cytotoxic T lymphocytes through T-cell receptor (TCR) recognition of the peptide-MHC complex.