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Title
IgE epitope proximity determines immune complex shape and effector cell activation capacity
AuthorValenta, Rudolf ; Finkelman, Fred D. ; Keller, Walter ; Focke-Tejkl, Margarete ; Weber, Milena ; Lupinek, Christian ; Cabauatan, Clarissa R. ; Zafred, Domen ; Khodoun, Marat ; Dutta, Moumita ; Roux, Kenneth H. ; Linhart, Birgit ; Gieras, Anna
Published in
Journal of Allergy and Clinical Immunology, New York, 2016, Vol. 137, Issue 5, page 1557-1565
PublishedNew York : Elsevier, 2016
LanguageEnglish
Document typeJournal Article
Keywords (EN)allergy / allergen / ige epitope / immune complex / effector cells / grass-pollen allergen / histamine-release / immunoglobulin-e / basophilic leukemia / mast-cells / responses / asthma / identification / degranulation / anaphylaxis
Project-/ReportnumberF 4605-B28
ISSN0091-6749
URNurn:nbn:at:at-ubmuw:3-1556 Persistent Identifier (URN)
DOI10.1016/j.jaci.2015.08.055 
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IgE epitope proximity determines immune complex shape and effector cell activation capacity [1.94 mb]
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Abstract (English)

Background: IgE-allergen complexes induce mast cell and basophil activation and thus immediate allergic inflammation. They are also important for IgE-facilitated allergen presentation to T cells by antigen-presenting cells. Objective: To investigate whether the proximity of IgE binding sites on an allergen affects immune complex shape and subsequent effector cell activation in vitro and in vivo. Methods: We constructed artificial allergens by grafting IgE epitopes in different numbers and proximity onto a scaffold protein. The shape of immune complexes formed between artificial allergens and the corresponding IgE was studied by negative-stain electron microscopy. Allergenic activity was determined using basophil activation assays. Mice were primed with IgE, followed by injection of artificial allergens to evaluate their in vivo allergenic activity. Severity of systemic anaphylaxis was measured by changes in body temperature. Results: We could demonstrate simultaneous binding of 4 IgE antibodies in close vicinity to each other. The proximity of IgE binding sites on allergens influenced the shape of the resulting immune complexes and the magnitude of effector cell activation and in vivo inflammation. Conclusions: Our results demonstrate that the proximity of IgE epitopes on an allergen affects its allergenic activity. We thus identified a novel mechanism by which IgE-allergen complexes regulate allergic inflammation. This mechanism should be important for allergy and other immune complex-mediated diseases.

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CC-BY-NC-ND-License (4.0)Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License