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

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• 作者：Anna Gieras ; PhD^a ; Birgit Linhart ; PhD^a ; Kenneth H. Roux ; PhD^b ; Moumita Dutta ; PhD^b ; Marat Khodoun ; PhD^c ; ^d ; ^e ; Domen Zafred ; PhD^f ; Clarissa R. Cabauatan ; PhD^a ; Christian Lupinek ; MD^a ; Milena Weber ; MSc^a ; Margarete Focke-Tejkl ; PhD^a ; Walter Keller ; PhD^f ; Fred D. Finkelman ; MD^c ; ^d ; ^e ; Rudolf Valenta ; MD^a ; ^{rudolf.valenta@meduniwien.ac.at" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Allergy ; allergen ; IgE epitope ; immune complex ; effector cells
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：137
• 期：5
• 页码：1557-1565
• 全文大小：1995 K

文摘

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.