Mouse Histocompatibility 2, D region, locus b (H-2Db) complexed with Premelanosome protein (gp100) peptide (25-33) (H-2Db-gp100(25-33))

H-2Db–gp100(25–33) is a peptide-major histocompatibility complex (pMHC) consisting of the mouse MHC class I molecule H-2Db and a specific 9-amino acid epitope (EGSRNQDWL) derived from the melanoma-associated antigen gp100 (Overwijk et al., 2003, Journal of Experimental Medicine). This complex is a critical target in preclinical immunology and oncology research, particularly in the study of T-cell responses against melanoma using the pmel-1 transgenic mouse model (Restifo et al., 2012, Nature Reviews Immunology). The gp100 protein, also known as PMEL, is a lineage-specific antigen expressed in melanocytes and overexpressed in most human and murine melanomas (Watt et al., 2013, Journal of Biological Chemistry). Recognition of this pMHC by specific CD8+ T-cell receptors (TCRs) triggers an immune response characterized by the release of cytotoxic granules and cytokines to eliminate tumor cells. Therapeutic strategies targeting this complex include peptide-based vaccines, adoptive cell transfer of TCR-engineered T cells, and the development of bispecific T-cell engagers. Because gp100 is also expressed in healthy melanocytes, targeting this complex can result in on-target, off-tumor toxicities such as vitiligo (Palmer et al., 2004, Journal of Immunology). This target is widely used to benchmark the efficacy of novel immunotherapies in syngeneic mouse tumor models like B16 melanoma.

Other names

H-2Db/gp100(25-33)gp100:25-33/H-2DbPMEL(25-33)/H-2DbEGSRNQDWL/H-2Db complexH-2Db-gp100 epitope

Recognition by specific CD8+ T-cell receptors (TCRs) leading to T-cell activation and cytotoxic lysis of antigen-presenting cells.