Allergen-specific IgE levels and the ability of IgE-allergen complexes to cross-link determine the extent of CD23-mediated T-cell activation

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:145

Article

Villazala-Merino, Sergio¹  Rodriguez-Dominguez, Azahara²  Stanek, Victoria¹  Campion, Nicholas J.¹  Gattinger, Pia²  Hofer, Gerhard⁷  Froeschl, Renate⁴  Fae, Ingrid⁵  Lupinek, Christian²  Vrtala, Susanne²  Breiteneder, Heimo³  Keller, Walter⁷  Perkmann, Thomas⁴  Nakamura, Ryosuke⁸  Pickl, Winfried F.⁶  Valenta, Rudolf^2,9,10  Eckl-Dorna, Julia¹  Niederberger, Verena¹ 

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

[2] Med Univ Vienna, Div Immunopathol, Vienna, Austria

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

[4] Med Univ Vienna, Dept Lab Med, Vienna, Austria

[5] Med Univ Vienna, Dept Blood Grp Serol & Transfus Med, Vienna, Austria

[6] Med Univ Vienna, Inst Immunol, Ctr Pathophysiol Infectiol & Immunol, Vienna, Austria

[7] Karl Franzens Univ Graz, Inst Mol Biosci, BioTechMed Graz, Graz, Austria

[8] Natl Inst Hlth Sci, Div Med Safety Sci, Kawasaki, Kanagawa, Japan

[9] Sechenov First Moscow State Med Univ, Immunopathol Lab, Dept Clin Immunol & Allergy, Moscow, Russia

[10] NRC Inst Immunol FMBA Russia, Moscow, Russia

关键词: Allergen;    CD23;    Bet v 1;    facilitated allergen presentation;    IgE;    birch pollen allergy;    cross-linking;    T-cell activation;    IgE-allergen complex;   

DOI  :  10.1016/j.jaci.2019.11.019

来源: Elsevier

【 摘 要 】

Background: CD23 mediates IgE-facilitated allergen presentation and subsequent allergen-specific T-cell activation in allergic patients. Objective: We sought to investigate key factors regulating IgE-facilitated allergen presentation through CD23 and subsequent T-cell activation. Methods: To study T-cell activation by free allergens and different types of IgE-Bet v 1 complexes, we used a molecular model based on monoclonal human Bet v 1-specific IgE, monomeric and oligomeric Bet v 1 allergen, an MHC-matched CD23-expressing B-cell line, and a T-cell line expressing a human Bet v 1-specific T-cell receptor. The ability to cross-link Fc epsilon receptors of complexes consisting of either IgE and monomeric Bet v 1 or IgE and oligomeric Bet v 1 was studied in human Fc epsilon RI-expressing basophils. T-cell proliferation by monomeric or oligomeric Bet v 1, which cross-links Fc epsilon receptors to a different extent, was studied in allergic patients' PBMCs with and without CD23-expressing B cells. Results: In our model non-cross-linking IgE-Bet v 1 monomer complexes, as well as cross-linking IgE-Bet v 1 oligomer complexes, induced T-cell activation, which was dependent on the concentration of specific IgE. However, T-cell activation by cross-linking IgE-Bet v 1 oligomer complexes was approximately 125-fold more efficient. Relevant T-cell proliferation occurred in allergic patients' PBMCs only in the presence of B cells, and its magnitude depended on the ability of IgE-Bet v 1 complexes to cross-link CD23. Conclusion: The extent of CD23-mediated T-cell activation depends on the concentration of allergen-specific IgE and the cross-linking ability of IgE-allergen complexes.

【 授权许可】

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