Critical and direct involvement of the CD23 stalk region in IgE binding

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:139

Article

Selb, Regina¹  Eckl-Dorna, Julia¹  Twaroch, Teresa E.²  Lupinek, Christian²  Teufelberger, Andrea^3,7  Hofer, Gerhard³  Focke-Tejkl, Margarete²  Gepp, Barbara⁴  Linhart, Birgit²  Breiteneder, Heimo⁴  Ellinger, Adolf⁵  Roux, Kenneth H.⁶  Valenta, Rudolf²  Niederberger, Verena¹ 

[1] Med Univ Vienna, Dept Otorhinolaryngol, Vienna, Austria

[2] Med Univ Vienna, Div Immunopathol, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria

[3] Karl Franzens Univ Graz, Inst Mol Biosci, Graz, Austria

[4] Med Univ Vienna, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Div Med Biotechnol, Vienna, Austria

[5] Med Univ Vienna, Dept Cell Biol & Ultrastruct Res, Ctr Anat & Cell Biol, Vienna, Austria

[6] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA

[7] Univ Hosp Ghent, Upper Airway Res Lab, Ghent, Belgium

关键词: CD23;    allergy;    IgE;    low-affinity IgE receptor;    B cell;    allergen;   

DOI  :  10.1016/j.jaci.2016.04.015

来源: Elsevier

【 摘 要 】

Background: The low-affinity receptor for IgE, FceRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration. Objective: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level. Methods: We expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated. The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism. By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed. Results: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23. Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FceRI, also inhibited IgE binding to CD23. Conclusion: Our results provide a new model for the CD23-IgE interaction. We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.

【 授权许可】

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