A glycopeptide in complex with MHC class I uses the GalNAc residue as an anchor

• DOI: 10.1073/pnas.2432220100
• Publication Date: 2003-12-09T18:17:48Z
• Authors: Vasso Apostolopoulos; Elizabeth Yuriev; Paul A. Ramsland; Jodie Halton; Carla Osinski; Wenjun Li; Magdalena Plebanski; Hans Paulsen; Ian F. C. McKenzie
• Keywords: Models, Molecular; Acetylgalactosamine; Binding Sites; Time Factors; Glycopeptides; Temperature; Genes, MHC Class I; Enzyme-Linked Immunosorbent Assay; Hydrogen Bonding; Protein Structure, Secondary; Mice, Inbred C57BL; Interferon-gamma; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Female; Peptides; Protein Binding

Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitroandin vivo) MUC1 glycopeptide (MUC1–8-5GalNAc) bound to H-2Kb, fully crossreactive with the nonglycosylated variant. Molecular modeling showed that the central P5-Thr-GalNAc residue points into the C pocket and forms van der Waals and hydrogen bond interactions with the MHC class I. As predicted, GalNAc, a modified peptide carrying an additional anchor in the central C anchor pocket, increased the affinity by ≈100-fold compared with the native low-affinity peptide (MUC1–8). The findings demonstrate that glycopeptides associated with MHC class I molecules can use GalNAc to anchor the peptide in the groove and enable high-affinity binding.