Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus

James P. Hewitson, James P. Hewitson, D. Linh Nguyen, Angela van Diepen, Cornelis H. Smit, Carolien A. Koeleman, Henry J. McSorley, Janice Murray, Rick M. Maizels, Cornelis H. Hokke

Research output: Contribution to journalArticlepeer-review

Abstract

Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory–secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. We used MALDI-TOF-MS and LC–MS/MS to analyse the repertoire of HES N- and O-linked glycans released by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1–4GlcNAc) structure, respectively. We also analysed the glycan repertoire of a major HES glycoprotein, VAL-2, which contains many glycan structures present in HES including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of HES, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host.
Original languageEnglish
Pages (from-to)157-170
Number of pages14
JournalInternational Journal For Parasitology
Volume46
Issue number3
Early online date12 Dec 2015
DOIs
Publication statusPublished - Mar 2016

Keywords

  • Heligmosomoides polygyrus
  • Antibody
  • Carbohydrate
  • Excretory-secretory product
  • Mass spectrometry
  • Nematode

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