Extended O-GlcNAc on HLA Class-I-Bound Peptides

Fabio Marino, Marshall Bern*, Geert P.M. Mommen, Aneika C. Leney, Jacqueline A.M. Van Gaans-Van Den Brink, Alexandre M.J.J. Bonvin, Christopher Becker, Cécile A.C.M. Van Els, Albert J.R. Heck

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


We report unexpected mass spectrometric observations of glycosylated human leukocyte antigen (HLA) class I-bound peptides. Complemented by molecular modeling, in vitro enzymatic assays, and oxonium ion patterns, we propose that the observed O-linked glycans carrying up to five monosaccharides are extended O-GlcNAc's rather than GalNAc-initiated O-glycans. A cytosolic O-GlcNAc modification is normally terminal and does not extend to produce a polysaccharide, but O-GlcNAc on an HLA peptide presents a special case because the loaded HLA class I complex traffics through the endoplasmic reticulum and Golgi apparatus on its way to the cell membrane and is hence exposed to glycosyltransferases. We also report for the first time natural HLA class I presentation of O- and N-linked glycopeptides derived from membrane proteins. HLA class I peptides with centrally located oligosaccharides have been shown to be immunogenic and may thus be important targets for immune surveillance.

Original languageEnglish
Pages (from-to)10922-10925
Number of pages4
JournalJournal of the American Chemical Society
Issue number34
Early online date17 Aug 2015
Publication statusPublished - 2 Sept 2015

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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