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

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

Journal

Xenotransplantation
ISSN: 0908-665X , E-ISSN: 1399-3089

Output data

Year: 2021, Volume: 28, Number: 3, Article number : 12672, Pages count : DOI: 10.1111/xen.12672

Authors

Dobrochaeva Kira ¹ , Khasbiullina Nailya ^2,3 , Shilova Nadezhda ^3,4,1 , Knirel Yuriy ² , Obukhova Polina ^3,1 , Nokel Alexey ^3,4 , Kunetskiy Roman ¹ , Tsygankova Svetlana ¹ , Bello-Gil Daniel ⁵ , Costa Cristina ⁵ , Mañez Rafael ⁵ , Bovin Nicolai ^6,1

Affiliations

1	Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
2	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
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, Russia
4	Semiotik LLC, Moscow, Russia
5	Infectious Pathology and Transplantation Division, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain
6	School of Engineering, Computer & Mathematical Sciences Auckland University of Technology Auckland New Zealand

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.

Dobrochaeva K. , Khasbiullina N. , Shilova N. , Knirel Y. , Obukhova P. , Nokel A. , Kunetskiy R. , Tsygankova S. , Bello-Gil D. , Costa C. , Mañez R. , Bovin N.
Specificity profile of αGal antibodies in αGalT KO mice as probed with comprehensive printed glycan array: Comparison with human anti‐Galili antibodies
Xenotransplantation. 2021. V.28. N3. 12672 . DOI: 10.1111/xen.12672 WOS Scopus OpenAlex

Web of science:	WOS:000606816500001
Scopus:	2-s2.0-85099251077
OpenAlex:	W3120297972

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