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A single glycan on IgE is indispensable for initiation of anaphylaxis

2015; Rockefeller University Press; Volume: 212; Issue: 4 Linguagem: Inglês

10.1084/jem.20142182

1540-9538

Kai-Ting Shade, Barbara Platzer, Nathaniel Washburn, V. Mani, Yannic C. Bartsch, Michelle E. Conroy, Jose D. Pagan, Carlos J. Bosques, Thorsten R. Mempel, Edda Fiebiger, Robert M. Anthony,

Urticaria and Related Conditions

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.