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

The gp100_25–33 peptide presented by MHC class I H-2Db is a critical antigenic target used in preclinical murine models of melanoma, particularly the B16 melanoma model (PubMed: 9841920). The peptide is derived from the Melanocyte protein PMEL (gp100), a type I transmembrane glycoprotein involved in melanosome biogenesis (UniProt: Q60696). The specific sequence EGSRNQDWL is processed and presented by the H-2Db MHC class I molecule on the surface of melanocytes and melanoma cells. This peptide-MHC complex is recognized by specific CD8+ T-cell receptors, making it a primary focus for developing and testing immunotherapies such as TCR-engineered T cells and peptide-based vaccines. Therapeutic targeting of this complex aims to induce a robust cytotoxic T-lymphocyte response against tumor cells. However, because gp100 is also expressed in normal melanocytes, treatment can lead to autoimmune-like side effects such as vitiligo and uveitis (PubMed: 12702466). This target remains a gold standard for evaluating the efficacy and safety of novel cancer immunotherapies in mouse models.

Other names

gp100:25-33/H-2DbPMEL:25-33/H-2DbEGSRNQDWL/H-2Db complexMelanocyte protein Pmel 17 peptide 25-33Silver locus protein peptide 25-33

The complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, which triggers the release of perforin and granzymes to induce apoptosis in the target cell (PubMed: 9841920).