Melanocyte protein PMEL (25-33) peptide presented by H-2Db (gp100(25-33)/H-2Db)

The gp100(25-33) peptide presented by H-2Db is a peptide-major histocompatibility complex (pMHC) that serves as a primary target for investigating T-cell-based immunotherapies in murine melanoma models (Overwijk et al., 2003, J. Exp. Med.). The epitope, consisting of the amino acid sequence EGSRNQDWL, is derived from the melanocyte-specific protein PMEL (gp100), which is involved in the maturation of melanosomes and is highly expressed in melanoma cells (UniProt P55015). This specific pMHC is recognized by the T-cell receptor (TCR) of Pmel-1 transgenic T cells, providing a robust system for studying adoptive cell transfer, T-cell memory, and vaccine efficacy (Restifo et al., 2012, Nat. Rev. Immunol.). Drugs and therapies targeting this complex, such as TCR-engineered T cells and peptide vaccines, aim to induce a potent cytotoxic T-lymphocyte (CTL) response against tumor cells (Klebanoff et al., 2005, PNAS). However, because gp100 is a differentiation antigen also present in healthy melanocytes, therapeutic targeting can lead to on-target, off-tumor autoimmune side effects, most commonly vitiligo and uveitis (Overwijk et al., 1999, PNAS). This target is essential for preclinical development of immunotherapeutic strategies and for understanding the balance between anti-tumor immunity and autoimmunity.

Other names

gp100(25-33)/H-2DbEGSRNQDWL/H-2Db complexPMEL(25-33)/H-2Dbgp100 epitopegp10025-33 peptide presented by H-2Db

T-cell receptor (TCR) binding to the pMHC complex, leading to the activation of CD8+ T-cell mediated cytotoxicity and IFN-gamma production.