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IgE epitope proximity determines immune complex shape and effector cell activation capacity.

Title: IgE epitope proximity determines immune complex shape and effector cell activation capacity.
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Name(s): Gieras, Anna, author
Linhart, Birgit, author
Roux, Kenneth H, author
Dutta, Moumita, author
Khodoun, Marat, author
Zafred, Domen, author
Cabauatan, Clarissa R, author
Lupinek, Christian, author
Weber, Milena, author
Focke-Tejkl, Margarete, author
Keller, Walter, author
Finkelman, Fred D, author
Valenta, Rudolf, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-05-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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. 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. 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. 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. 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.
Identifier: FSU_pmch_26684291 (IID), 10.1016/j.jaci.2015.08.055 (DOI), PMC4890651 (PMCID), 26684291 (RID), 26684291 (EID), S0091-6749(15)01422-0 (PII)
Keywords: Allergy, IgE epitope, Allergen, Effector cells, Immune complex
Grant Number: F 4605
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890651.
Subject(s): Allergens/genetics
Allergens/immunology
Anaphylaxis/immunology
Animals
Antigen-Antibody Complex/immunology
Epitopes/immunology
Immunoglobulin E/immunology
Mice, Inbred BALB C
Myoglobin/genetics
Myoglobin/immunology
Plant Proteins/genetics
Plant Proteins/immunology
Recombinant Proteins/immunology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26684291
Owner Institution: FSU
Is Part Of: The Journal of allergy and clinical immunology.
1097-6825
Issue: iss. 5, vol. 137

Choose the citation style.
Gieras, A., Linhart, B., Roux, K. H., Dutta, M., Khodoun, M., Zafred, D., … Valenta, R. (2016). IgE epitope proximity determines immune complex shape and effector cell activation capacity. The Journal Of Allergy And Clinical Immunology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26684291