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Specificity of human natural antibodies referred to as anti-Tn

Abstract : 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 con-formationally 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.
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Submitted on : Monday, March 30, 2020 - 10:20:32 AM
Last modification on : Tuesday, July 14, 2020 - 11:04:09 AM

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Kira Dobrochaeva, Nailya Khasbiullina, Nadezhda Shilova, Nadezhda Antipova, Polina Obukhova, et al.. Specificity of human natural antibodies referred to as anti-Tn. Molecular Immunology, Elsevier, 2020, 120, pp.74-82. ⟨10.1016/j.molimm.2020.02.005⟩. ⟨inserm-02524088⟩

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