Specificity of human natural antibodies referred to as anti-Tn

Specificity of human natural antibodies referred to as anti-Tn Full article

Journal

Molecular Immunology
ISSN: 0161-5890 , E-ISSN: 1872-9142

Output data

Year: 2020, Volume: 120, Pages: 74-82 Pages count : 9 DOI: 10.1016/j.molimm.2020.02.005

Authors

Dobrochaeva Kira ¹ , Khasbiullina Nailya ^2,3,4 , Shilova Nadezhda ^2,3,1 , Antipova Nadezhda ^5,6,1 , Obukhova Polina ^2,1 , Ovchinnikova Tatiana ¹ , Galanina Oxana ¹ , Blixt Ola ⁷ , Kunz Horst ⁸ , Filatov Alexander ⁹ , Knirel Yuriy ⁴ , LePendu Jacques ¹⁰ , Khaidukov Sergey ¹ , Bovin Nicolai ¹

Affiliations

1	Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russian Federation
2	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
3	Semiotik LLC, 16/10 Miklukho-Maklaya, Moscow, 117997, Russian Federation
4	Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russian Federation
5	National Research University Higher School of Economics, Moscow 101000, Russian Federation
6	Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya, Moscow 117198, Russian Federation
7	Department of Chemistry, Chemical Biology, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark
8	Institut Für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, D-55128, Mainz, Germany
9	Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, 115478, Russian Federation
10	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.

Dobrochaeva K. , Khasbiullina N. , Shilova N. , Antipova N. , Obukhova P. , Ovchinnikova T. , Galanina O. , Blixt O. , Kunz H. , Filatov A. , Knirel Y. , LePendu J. , Khaidukov S. , Bovin N.
Specificity of human natural antibodies referred to as anti-Tn
Molecular Immunology. 2020. V.120. P.74-82. DOI: 10.1016/j.molimm.2020.02.005 WOS Scopus OpenAlex

Web of science:	WOS:000528191400009
Scopus:	2-s2.0-85079548958
OpenAlex:	W3007772679

DB	Citing
OpenAlex	24
Scopus	23
Web of science	21