title: A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors.
abstract: Immunoglobulin G (IgG) glycosylation modulates antibody activity and represents a major source of heterogeneity within antibody preparations. Depending on their glycosylation pattern, individual IgG glycovariants present in recombinant antibody preparations may trigger effects ranging from enhanced pro-inflammatory activity to increased anti-inflammatory activity. In contrast, reduction of IgG glycosylation beyond the central mannose core is generally believed to result in impaired IgG activity. However, this study reveals that a mono- or disaccharide structure consisting of one N-acetylglucosamine with or without a branching fucose residue is sufficient to retain the activity of the most active human and mouse IgG subclasses in vivo and further directs antibody activity to cellular Fcγ receptors. Notably, the activity of minimally glycosylated antibodies is not predicted by in vitro assays based on a monomeric antibody-Fcγ-receptor interaction analysis, whereas in vitro assay systems using immune complexes are more suitable to predict IgG activity in vivo.
authors.affiliation: Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kao
authors.affiliation: Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Danzer
authors.affiliation: Department of Clinical Sciences, Division of Infection Medicine, Biomedical Center B14, Lund University, 221 84 Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Collin
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Schuhstrasse 19, 91052 Erlangen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Groß
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Schuhstrasse 19, 91052 Erlangen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Eichler
authors.affiliation: Genos Glycoscience Research Laboratory, Hondlova 2/11, 10000 Zagreb, Croatia.
authors.forename: Jerko
authors.initials: J
authors.lastname: Stambuk
authors.affiliation: Genos Glycoscience Research Laboratory, Hondlova 2/11, 10000 Zagreb, Croatia.
authors.forename: Gordan
authors.initials: G
authors.lastname: Lauc
authors.affiliation: Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Lux
authors.affiliation: Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, Germany. Electronic address: falk.nimmerjahn@fau.de.
authors.forename: Falk
authors.initials: F
authors.lastname: Nimmerjahn
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology; D016466:CHO Cells; D045744:Cell Line, Tumor; D015922:Complement C1q / Q000737:chemistry / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006020:Glycopeptides / Q000032:analysis; D006026:Glycoside Hydrolases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009005:Monosaccharides / Q000378:metabolism*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D011485:Protein Binding; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics
chemical_list: D018951:Antigens, CD20; C485701:Fcgr1 protein, mouse; D006020:Glycopeptides; D007074:Immunoglobulin G; D009005:Monosaccharides; D011961:Receptors, Fc; D017452:Receptors, IgG; D015922:Complement C1q; D006026:Glycoside Hydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
keywords: Fcγ receptors; IgG; cytotoxic antibodies; glycosylation