Variable Domain N-Linked Glycans Acquired During Antigen-Specific Immune Responses Can Contribute to Immunoglobulin G Antibody Stability

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ID: 73334
2018
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Abstract
Immunoglobulin G (IgG) can contain N-linked glycans in the variable domains, the so-called Fab glycans, in addition to the Fc glycans in the CH2 domains. These Fab glycans are acquired following introduction of N-glycosylation sites during somatic hypermutation and contribute to antibody diversification. We investigated whether Fab glycans may—in addition to affecting antigen binding—contribute to antibody stability. By analyzing thermal unfolding profiles of antibodies with or without Fab glycans, we demonstrate that introduction of Fab glycans can improve antibody stability. Strikingly, removal of Fab glycans naturally acquired during antigen-specific immune responses can deteriorate antibody stability, suggesting in vivo selection of stable, glycosylated antibodies. Collectively, our data show that variable domain N-linked glycans acquired during somatic hypermutation can contribute to IgG antibody stability. These findings indicate that introducing Fab glycans may represent a mechanism to improve therapeutic/diagnostic antibody stability.
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bovenkamp2018variablefrontiers Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Bovenkamp, Fleur S. van de;Bovenkamp, Fleur S. van de;Derksen, Ninotska I. L.;Derksen, Ninotska I. L.;Breemen, Mariëlle J. van;Taeye, Steven W. de;Taeye, Steven W. de;Taeye, Steven W. de;Heer, Pleuni Ooijevaar-de;Heer, Pleuni Ooijevaar-de;Sanders, Rogier W.;Sanders, Rogier W.;Rispens, Theo;Rispens, Theo;
Journal Frontiers in immunology
Year 2018
DOI
DOI not found
URL
http://journal.frontiersin.org/article/10.3389/fimmu.2018.00740/full
Keywords
Veterinary medicine Medicine (General) Medicine Science Immunologic diseases. Allergy genetics animal culture

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