A single glycan on IgE is indispensable for initiation of anaphylaxis.

Abstract

Immunoglobulin ε (IgE) antibodies are the primary mediators of allergic diseases, which affect more than 1 in 10 individuals worldwide. IgE specific for innocuous environmental antigens, or allergens, binds and sensitizes tissue-resident mast cells expressing the high-affinity IgE receptor, FcεRI. Subsequent allergen exposure cross-links mast cell-bound IgE, resulting in the release of inflammatory mediators and initiation of the allergic cascade. It is well established that precise glycosylation patterns exert profound effects on the biological activity of IgG. However, the contribution of glycosylation to IgE biology is less clear. Here, we demonstrate an absolute requirement for IgE glycosylation in allergic reactions. The obligatory glycan was mapped to a single N-linked oligomannose structure in the constant domain 3 (Cε3) of IgE, at asparagine-394 (N394) in human IgE and N384 in mouse. Genetic disruption of the site or enzymatic removal of the oligomannose glycan altered IgE secondary structure and abrogated IgE binding to FcεRI, rendering IgE incapable of eliciting mast cell degranulation, thereby preventing anaphylaxis. These results underscore an unappreciated and essential requirement of glycosylation in IgE biology.

• Authors: Kai-Ting C Shade, Barbara Platzer, Nathaniel Washburn, Vinidhra Mani, Yannic C Bartsch, Michelle Conroy, Jose D Pagan, Carlos Bosques, Thorsten R Mempel, Edda Fiebiger, Robert M Anthony
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 212 Issue 4 Pg. 457-67 (Apr 06 2015) ISSN: 1540-9538 [Electronic] United States
• PMID: 25824821 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2015 Shade et al.

Chemical References

• Immunoglobulin Constant Regions
• Inflammation Mediators
• Polysaccharides
• Receptors, IgE
• Immunoglobulin E

Topics

• Anaphylaxis (genetics, immunology, pathology, prevention & control)
• Animals
• Cell Degranulation (genetics, immunology)
• Glycosylation
• Humans
• Immunoglobulin Constant Regions (genetics, immunology)
• Immunoglobulin E (genetics, immunology)
• Inflammation Mediators
• Mast Cells (immunology, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Polysaccharides (genetics, immunology)
• Receptors, IgE (genetics, immunology)