title: A glycopeptide in complex with MHC class I uses the GalNAc residue as an anchor.
abstract: Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitro and in 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 approximately 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.
authors.affiliation: The Austin Research Institute, Heidelberg VIC 3084, Australia. v.apostolopoulos@ari.unimelb.edu.au
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yuriev
authors.forename: Paul A
authors.initials: PA
authors.lastname: Ramsland
authors.forename: Jodie
authors.initials: J
authors.lastname: Halton
authors.forename: Carla
authors.initials: C
authors.lastname: Osinski
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
authors.forename: Hans
authors.initials: H
authors.lastname: Paulsen
authors.forename: Ian F C
authors.initials: IF
authors.lastname: McKenzie
mesh_terms: D000116:Acetylgalactosamine / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005805:Genes, MHC Class I; D006020:Glycopeptides / Q000737:chemistry*; D006860:Hydrogen Bonding; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013696:Temperature; D013997:Time Factors
chemical_list: D006020:Glycopeptides; D010455:Peptides; D007371:Interferon-gamma; D000116:Acetylgalactosamine