A glycopeptide in complex with MHC class I uses the GalNAc residue as an anchor.
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.
Apostolopoulos
Vasso
V
The Austin Research Institute, Heidelberg VIC 3084, Australia. v.apostolopoulos@ari.unimelb.edu.au
Yuriev
Elizabeth
E
Ramsland
Paul A
PA
Halton
Jodie
J
Osinski
Carla
C
Li
Wenjun
W
Plebanski
Magdalena
M
Paulsen
Hans
H
McKenzie
Ian F C
IF
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
D006020:Glycopeptides; D010455:Peptides; D007371:Interferon-gamma; D000116:Acetylgalactosamine