Major histocompatibility complex class I – Tyrosinase-related protein 2 complex (MHC I-TRP2)

The Major histocompatibility complex class I – Tyrosinase-related protein 2 (MHC I-TRP2) complex is a primary immunological target in the treatment of melanoma [1]. TRP2, also known as dopachrome tautomerase (DCT), is an enzyme involved in melanin synthesis that is highly expressed in melanocytes and melanoma cells [2]. The complex forms when TRP2-derived peptides are processed and loaded into the MHC class I binding groove for presentation on the cell surface [3]. This presentation allows CD8+ cytotoxic T lymphocytes to recognize and eliminate tumor cells through T-cell receptor (TCR) binding [4]. Therapeutic strategies targeting this complex include peptide and DNA vaccines, such as SCIB1, which aim to expand the population of TRP2-specific T cells [5]. Additionally, engineered TCR-T cell therapies are being developed to specifically bind the MHC I-TRP2 complex with high affinity [6]. A significant challenge in targeting this complex is the potential for autoimmune vitiligo, as the immune system may also attack healthy melanocytes expressing TRP2 [5].

Other names

HLA-A*02:01-TRP2 complexH-2Kb-TRP2 complexMHC-TRP2 peptide complexDopachrome tautomerase epitope-MHC complexTRP-2/HLA-A2 complexMHC class I – TRP2 epitope binding groove

Presentation of Tyrosinase-related protein 2 (TRP2) epitopes to CD8+ T cells via MHC class I molecules to induce a targeted cytotoxic immune response against melanoma cells [1, 4].