Specificity of human natural antibodies referred to as anti-Tn

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. © 2020 Elsevier Ltd

Dobrochaeva K.1 , Khasbiullina N.2, 3, 7 , Shilova N.1, 2, 3 , Antipova N. 1, 9, 10 , Obukhova P.1, 3 , Ovchinnikova T.1 , Galanina O.1 , Blixt O.4 , Kunz H.5 , Filatov A.6 , Knirel Y.7 , LePendu J.8 , Khaidukov S. 1 , Bovin N.1
Elsevier Ltd
  • 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russian Federation
  • 2 Semiotik LLC, 16/10 Miklukho-Maklaya, Moscow, 117997, Russian Federation
  • 3 National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, 117997, Russian Federation
  • 4 Department of Chemistry, Chemical Biology, University of Copenhagen, Thorvaldsensvej 40, Frederiksberg C, 1871, Denmark
  • 5 Institut Für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, Mainz, D-55128, Germany
  • 6 Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, 115478, Russian Federation
  • 7 Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991, Russian Federation
  • 8 University of Nantes, Inserm, U892 IRT UN, 8 Quai MonCousu, BP70721 NantesFR 44007, France
  • 9 Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya, Moscow, 117198, Russian Federation
  • 10 National Research University Higher School of Economics, Moscow, 101000, Russian Federation
Anti-Glycan antibodies; Cancer; Glycans; Natural antibodies; Tn antigen
Date of creation
Date of change
Short link

Other records