Glycoprotein 100 peptide–Histocompatibility 2-Db complex (gp100–H-2Db)

The Glycoprotein 100 (gp100) peptide–Histocompatibility 2-Db (H-2Db) complex is a peptide-major histocompatibility complex (pMHC) that plays a central role in murine melanoma immunology research (Overwijk et al., 2003, J. Exp. Med.). It consists of a processed peptide from the gp100 protein (also known as PMEL), typically the gp100:25-33 sequence (EGSRNQDWL), presented on the cell surface by the H-2Db MHC class I molecule (Restifo et al., 2012, Nat. Rev. Immunol.). This complex is specifically recognized by the Pmel-1 T-cell receptor (TCR), making it a foundational model for studying adoptive cell transfer and the mechanisms of T-cell-mediated tumor regression (UniProt Q60696). In therapeutic development, this complex is targeted by vaccines and TCR-engineered T cells to induce a cytotoxic immune response against melanoma cells. However, because gp100 is also expressed in healthy melanocytes, targeting this complex can result in on-target, off-tumor toxicities such as vitiligo and uveitis (PubMed: 12913096). The complex is a critical tool for evaluating the potency and safety of immunotherapies before they transition to human HLA-A2-restricted gp100 targets.

Other names

gp100–H-2Db complexPMEL peptide–H-2Db complexgp100(25-33)–H-2DbPmel-1 target complexgp100:25-33–H-2Db

The complex acts as a specific ligand for CD8+ T-cell receptors (TCRs); binding of a cognate TCR to the gp100–H-2Db complex triggers a signaling cascade that leads to T-cell activation, cytokine release, and the directed lysis of the antigen-presenting cell.