Specificity profile of αGal antibodies in αGalT KO mice as probed with comprehensive printed glycan array: Comparison with human anti-Galili antibodies.

Autor: Dobrochaeva K; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia., Khasbiullina N; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia.; National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, Russia., Shilova N; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, Russia.; Semiotik LLC, Moscow, Russia., Knirel Y; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia., Obukhova P; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, Russia., Nokel A; National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Moscow, Russia.; Semiotik LLC, Moscow, Russia., Kunetskiy R; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia., Tsygankova S; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia., Bello-Gil D; Infectious Pathology and Transplantation Division, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain., Costa C; Infectious Pathology and Transplantation Division, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain., Mañez R; Infectious Pathology and Transplantation Division, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain., Bovin N; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.; School of Engineering, Computer & Mathematical Sciences, Auckland University of Technology, Auckland, New Zealand.
Jazyk: angličtina
Zdroj: Xenotransplantation [Xenotransplantation] 2021 May; Vol. 28 (3), pp. e12672. Date of Electronic Publication: 2021 Jan 12.
DOI: 10.1111/xen.12672
Abstrakt: Background: The α1,3-galactosyltransferase gene-knockout (GalT KO) mice are able to produce natural anti-αGal antibodies apparently without any specific immunization. GalT KO mice are commonly used as a model immunological system for studying anti-αGal responses to Gal-positive xenografts in human. In this study, we compared the specificity of mouse and human αGal antibodies to realize the adequacy of the murine model.
Methods: Using hapten-specific affinity chromatography antibodies against Galα1-3Galβ1-4GlcNAcβ epitope were isolated from both human and GalT KO mice blood sera. Specificity of isolated antibodies was determined using a printed glycan array (PGA) containing 400 mammalian glycans and 200 bacterial polysaccharides.
Results: The quantity of isolated specific anti-Galα antibodies corresponds to a content of <0.2% of total Ig, which is an order of magnitude lower than that generally assumed for both human and murine peripheral blood immunoglobulin, with a high predominance of IgM over IgG (95% vs 5%). Analysis using a printed glycan array has demonstrated that (a) antibodies from both species bind not only the Galα1-3Galβ1-4GlcNAcβ epitope, but also unrelated glycans; (b) particularly, for human (but not mouse) antibodies the best binders appear to be bacterial polysaccharides; (c) the profile of mouse antibodies is broader, it is noteworthy that they recognize a variety of human blood group B epitopes and even glycans without the α-galactosyl residue.
Conclusions: We believe that the mouse model should be used cautiously in xenotransplantation experiments when the fine epitope specificity of antibodies is critical.
(© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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