The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites

Christoph Schneider, David F. Smith, Richard D. Cummings, Kayluz Frias Boligan, Robert G. Hamilton, Bruce Scott Bochner, Sylvia Miescher, Hans Uwe Simon, Anastas Pashov, Tchavdar Vassilev, Stephan Von Gunten

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 systemslevel 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.

Original languageEnglish (US)
Article number269ra1
JournalScience Translational Medicine
Volume7
Issue number269
DOIs
StatePublished - Jan 1 2015

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Polysaccharides
Immunoglobulin G
Carbohydrates
Antibodies
Microbiological Attachment Sites
Tumor-Associated Carbohydrate Antigens
T Independent Antigens
T-Lymphocytes
Antigens
Exotoxins
Systems Biology
Intravenous Immunoglobulins
Vaccines
Technology
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Schneider, Christoph ; Smith, David F. ; Cummings, Richard D. ; Boligan, Kayluz Frias ; Hamilton, Robert G. ; Bochner, Bruce Scott ; Miescher, Sylvia ; Simon, Hans Uwe ; Pashov, Anastas ; Vassilev, Tchavdar ; Von Gunten, Stephan. / The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites. In: Science Translational Medicine. 2015 ; Vol. 7, No. 269.
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Schneider, C, Smith, DF, Cummings, RD, Boligan, KF, Hamilton, RG, Bochner, BS, Miescher, S, Simon, HU, Pashov, A, Vassilev, T & Von Gunten, S 2015, 'The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites' Science Translational Medicine, vol. 7, no. 269, 269ra1. https://doi.org/10.1126/scitranslmed.3010524

The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites. / Schneider, Christoph; Smith, David F.; Cummings, Richard D.; Boligan, Kayluz Frias; Hamilton, Robert G.; Bochner, Bruce Scott; Miescher, Sylvia; Simon, Hans Uwe; Pashov, Anastas; Vassilev, Tchavdar; Von Gunten, Stephan.

In: Science Translational Medicine, Vol. 7, No. 269, 269ra1, 01.01.2015.

Research output: Contribution to journalArticle

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