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Specificity profile of αGal antibodies in αGalT KO mice as probed with comprehensive printed glycan array: Comparison with human anti‐Galili antibodies
Author(s) -
Dobrochaeva Kira,
Khasbiulliilya,
Shilova Nadezhda,
Knirel Yuriy,
Obukhova Polina,
Nokel Alexey,
Kunetskiy Roman,
Tsygankova Svetlana,
BelloGil Daniel,
Costa Cristina,
Mañez Rafael,
Bovin Nicolai
Publication year - 2021
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12672
Subject(s) - antibody , epitope , xenotransplantation , glycan , microbiology and biotechnology , biology , immunization , glycoprotein , immunology , transplantation , medicine , surgery
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.