Publications & Reports

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

Apostolopoulos V, Yuriev E, Ramsland PA, Halton J, Osinski C, Li W, Plebanski M, Paulsen H, McKenzie IF
The Austin Research Institute, Heidelberg VIC 3084, Australia. v.apostolopoulos@ari.unimelb.edu.au

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.

Publication

  • Journal: Proceedings of the National Academy of Sciences of the United States of America
  • Published: 09/12/2003
  • Volume: 100
  • Issue: 25
  • Pagination: 15029-15034