Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus. Issue 3 (March 2016)

• Record Type: Journal Article
• Authors: Hewitson, James P.; Nguyen, D. Linh; van Diepen, Angela; Smit, Cornelis H.; Koeleman, Carolien A.; McSorley, Henry J.; Murray, Janice; Maizels, Rick M.; Hokke, Cornelis H.
• Is Part Of: International journal for parasitology. Volume 46:Issue 3(2016)
• Page Start: 157
• Page End: 170
• Publication Date: 2016-03
• Subjects: Nematode -- Heligmosomoides polygyrus -- Carbohydrate -- Mass spectrometry -- Excretory–secretory product -- Antibody; Parasitology -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; Parasitology; Periodicals; Electronic journals; 571.999
• DOI: 10.1016/j.ijpara.2015.10.004
• Languages: English
• ISSNs: 0020-7519

Abstract

Graphical abstract: Highlights: Heligmosomoides polygyrus excretory–secretory (ES) proteins carry diverse N - and O -glycans, and many are O -methylated. A methylhexose containing O -glycan of abundant ES glycoproteins is immunodominant. This dominant glycan is not the immunomodulatory heat-stable ES component. 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 N - and O -linked glycans released from Heligmosomoides polygyrus excretory–secretory products 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 glycoprotein in Heligmosomoides polygyrus excretory–secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory–secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory–secretory products, 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.