Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Selb, R; Eckl-Dorna, J; Twaroch, TE; Lupinek, C; Teufelberger, A; Hofer, G; Focke-Tejkl, M; Gepp, B; Linhart, B; Breiteneder, H; Ellinger, A; Keller, W; Roux, KH; Valenta, R; Niederberger, V.
Critical and direct involvement of the CD23 stalk region in IgE binding.
J Allergy Clin Immunol. 2017; 139(1): 281-289.
Doi: 10.1016/j.jaci.2016.04.015
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- Co-Autor*innen der Med Uni Graz
- Teufelberger Andrea Renate
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- Abstract:
- The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration. 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. 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. 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 FcεRI, also inhibited IgE binding to CD23. 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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, Plant - immunology
- Binding Sites -
- Cell Line -
- Humans -
- Immunoglobulin E - immunology
- Insecta -
- Omalizumab - pharmacology
- Protein Binding - drug effects
- Receptors, IgE - chemistry
- Receptors, IgE - immunology
- Find related publications in this database (Keywords)
- CD23
- allergy
- IgE
- low-affinity IgE receptor
- B cell
- allergen