Human natural antibodies recognizing glycan galβ1-3glcnac (LeC)

The level of human natural antibodies of immunoglobulin M isotype against LeC in patients with breast cancer is lower than in healthy women. The epitope specificity of these antibodies has been characterized using a printed glycan array and enzyme-linked immunosorbent assay (ELISA), the antibodies being isolated from donors’ blood using LeC-Sepharose (LeC is Galβ1-3GlcNAcβ). The isolated antibodies recognize the disaccharide but do not bind to glycans terminated with LeC, which implies the impossibility of binding to regular glycoproteins of non-malignant cells. The avidity (as dissociation constant value) of antibodies probed with a multivalent disaccharide is 10−9 M; the nanomolar level indicates that the concentration is sufficient for physiological binding to the cognate antigen. Testing of several breast cancer cell lines showed the strongest binding to ZR 75-1. Interestingly, only 7% of the cells were positive in a monolayer with a low density, increasing up to 96% at highest density. The enhanced interaction (instead of the expected inhibition) of antibodies with ZR 75-1 cells in the presence of Galβ1-3GlcNAcβ disaccharide, indicates that the target epitope of anti-LeC antibodies is a molecular pattern with a carbohydrate constituent rather than a glycan. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Authors
Dobrochaeva K.1 , Khasbiullina N.2, 3, 4 , Shilova N.1, 2, 3 , Antipova N. 1, 5, 6 , Obukhova P.1, 3 , Galanina O.1 , Gorbach M.1 , Popova I.1 , Khaidukov S. 1 , Grishchenko N.7 , Tupitsyn N.7 , Pendu J.L.8 , Bovin N.1, 9
Publisher
MDPI AG
Number of issue
18
Language
English
Pages
1-15
Status
Published
Number
6511
Volume
21
Year
2020
Organizations
  • 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, 4 Oparin str, Moscow, 117997, Russian Federation
  • 4 N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky pr, Moscow, 119991, Russian Federation
  • 5 Peoples’Friendship, University of Russia (RUDN), 6 Miklukho-Maklaya, Moscow, 117198, Russian Federation
  • 6 National Research University Higher School of Economics, Moscow, 101000, Russian Federation
  • 7 N.N.Blokhin Russian Cancer Research Centre оf the Ministry of Healthcare of Russian Federation, 24 Kashyrskoe Sh., Moscow, 115478, Russian Federation
  • 8 CRCINA, INSERM, Université d’Angers, Université de Nantes, 8 quai Moncousu, Nantes, 70721-44007, France
  • 9 Centre for Kode Technology Innovation, Auckland University of Technology, 55 Wellesley Street East, Auckland, 1010, New Zealand
Keywords
Breast cancer; Cancer-associated antibodies; LeC antigen; Natural anti-glycan antibodies; Printed glycan array
Date of creation
02.11.2020
Date of change
02.11.2020
Short link
https://repository.rudn.ru/en/records/article/record/64407/
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