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Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11: XN6P4

]

NCBI PubMed ID: 32087569
Publication DOI: 10.1016/j.molimm.2020.02.005
Journal NLM ID: 7905289
Publisher: Elsevier
Correspondence: professorbovin

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Institutions: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, Russian Federation, Semiotik LLC, 16/10 Miklukho-Maklaya, Moscow, Russian Federation, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, Russian Federation, National Research University Higher School of Economics, Moscow, Russian Federation, Department of Chemistry, Chemical Biology, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark, Institut Fur Organische Chemie, Johannes Gutenberg-Universitat Mainz, Duesbergweg 10-14, D-55128, Mainz, Germany, Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russian Federation, University of Nantes, Inserm, U892 IRT UN, 8 Quai MonCousu, BP70721 Nantes, FR 44007, France

To understand the role of human natural IgM known as antibodies against the carbohydrate epitope Tn, the antibodies were isolated using GalNAcα-Sepharose affinity chromatography, and their specificity was profiled using microarrays (a glycan array printed with oligosaccharides and bacterial polysaccharides, as well as a glycopeptide array), flow cytometry, and inhibition ELISA. The antibodies bound a restricted number of GalNAcα-terminated oligosaccharides better than the parent monosaccharide, e.g., 6-O-Su-GalNAcα and GalNAcα1-3Galβ1-3(4)GlcNAcβ. The binding with several bacterial polysaccharides that have no structural resemblance to the affinity ligand GalNAcα was quite unexpected. Given that GalNAcα is considered the key fragment of the Tn antigen, it is surprising that these antibodies bind weakly GalNAcα-OSer and do not bind a wide variety of GalNAcα-OSer/Thr-containing mucin glycopeptides. At the same time, we have observed specific binding to cells having Tn-positive glycoproteins containing similar glycopeptide motifs in a conformationally rigid macromolecule. Thus, specific recognition of the Tn antigen apparently requires that the naturally occurring "anti-Tn" IgM recognize a complex epitope comprising the GalNAcα as an essential component and a fairly long amino acid sequence where the amino acids adjacent to GalNAcα do not contact the antibody paratope; i.e., the antibodies recognize a spatial epitope or a molecular pattern rather than a classical continuous sequence. In addition, we have not found any increase in the binding of natural antibodies when GalNAcα residues were clustered. These results may help in further development of anticancer vaccines based on synthetic Tn constructs.

cancer, glycans, natural antibodies, anti-glycan antibodies, Tn antigen

Structure type: suggested polymer biological repeating unit
Location inside paper: table S1, E. coli O119 (GID 1217)
Compound class: O-polysaccharide, O-antigen
Contained glycoepitopes: IEDB_136105,IEDB_136906,IEDB_137472,IEDB_137485,IEDB_141794,IEDB_141807,IEDB_144983,IEDB_151528,IEDB_151531,IEDB_152206,IEDB_190606,IEDB_225177,IEDB_885823,IEDB_983930,SB_44,SB_7,SB_72

Methods: ELISA, affinity chromatography, flow cytometry analysis, printed glycan array (PGA) analysis, FACS assay
Comments, role: the list of bacterial polysaccharides used in printed glycan array (PGA) is presented in table S1.

NCBI Taxonomy refs (TaxIDs): 1450174
Reference(s) to other database(s): GTC:G83232MC, GlycomeDB:28121
Show glycosyltransferases

There is only one chemically distinct structure:

[*]O[C@@H]1[C@H](O[C@H]2[C@@H](O)[C@@H](CO)O[C@H](O[C@H]3[C@H](C)O[C@@H](O[C@@H]4[C@@H](NC(C)=O)[C@@H]([*])O[C@H](CO)[C@H]4O)[C@H](O)[C@@H]3O)[C@@H]2O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1O[C@@H](C)[C@H](O)[C@@H](NC=O)[C@H]1NC(C)=O

SVG MW SMILES 3D mol Ionize