title: The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites.
abstract: Despite the paradigm that carbohydrates are T cell-independent antigens, isotype-switched glycan-specific immunoglobulin G (IgG) antibodies and polysaccharide-specific T cells are found in humans. We used a systems-level approach combined with glycan array technology to decipher the repertoire of carbohydrate-specific IgG antibodies in intravenous and subcutaneous immunoglobulin preparations. A strikingly universal architecture of this repertoire with modular organization among different donor populations revealed an association between immunogenicity or tolerance and particular structural features of glycans. Antibodies were identified with specificity not only for microbial antigens but also for a broad spectrum of host glycans that serve as attachment sites for viral and bacterial pathogens and/or exotoxins. Tumor-associated carbohydrate antigens were differentially detected by IgG antibodies, whereas non-IgG2 reactivity was predominantly absent. Our study highlights the power of systems biology approaches to analyze immune responses and reveals potential glycan antigen determinants that are relevant to vaccine design, diagnostic assays, and antibody-based therapies.
authors.affiliation: Institute of Pharmacology, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schneider
authors.affiliation: Protein-Carbohydrate Interaction Core H, Consortium for Functional Glycomics, Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Smith
authors.affiliation: Protein-Carbohydrate Interaction Core H, Consortium for Functional Glycomics, Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Cummings
authors.affiliation: Institute of Pharmacology, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Kayluz Frias
authors.initials: KF
authors.lastname: Boligan
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hamilton
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bochner
authors.affiliation: Research and Development, CSL Behring AG, CH-3014 Bern, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Miescher
authors.affiliation: Institute of Pharmacology, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
authors.affiliation: Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Anastas
authors.initials: A
authors.lastname: Pashov
authors.affiliation: Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
authors.forename: Tchavdar
authors.initials: T
authors.lastname: Vassilev
authors.affiliation: Institute of Pharmacology, University of Bern, CH-3010 Bern, Switzerland. stephan.vongunten@pki.unibe.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Gunten
mesh_terms: D000918:Antibody Specificity / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001287:Attachment Sites, Microbiological / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D054794:Glycomics; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000276:immunology; D008024:Ligands; D014019:Tissue Donors
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D002241:Carbohydrates; D000939:Epitopes; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008024:Ligands