Mapping of the CD23 Binding Site on Immunoglobulin E (IgE) and Allosteric Control of the IgE-Fc epsilon RI Interaction

Susmita Borthakur, Richard G. Hibbert, Marie O. Y. Pang, Norhakim Yahya, Heather J. Bax, Michael W. Kao, Alison M. Cooper, Andrew J. Beavil, Brian J. Sutton, Hannah J. Gould, James M. McDonnell

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

IgE, the antibody that mediates allergic responses, acts as part of a self-regulating protein network. Its unique effector functions are controlled through interactions of its Fc region with two cellular receptors, Fc epsilon RI on mast cells and basophils and CD23 on B cells. IgE cross-linked by allergen triggers mast cell activation via Fc epsilon RI, whereas IgE-CD23 interactions control IgE expression levels. We have determined the CD23 binding site on IgE, using a combination of NMR chemical shift mapping and site-directed mutagenesis. We show that the CD23 and Fc epsilon RI interaction sites are at opposite ends of the C epsilon 3 domain of IgE, but that receptor binding is mutually inhibitory, mediated by an allosteric mechanism. This prevents CD23-mediated cross-linking of IgE bound to Fc epsilon RI on mast cells and resulting antigen-independent anaphylaxis. The mutually inhibitory nature of receptor binding provides a degree of autonomy for the individual activities mediated by IgE-Fc epsilon RI and IgE-CD23 interactions.

Original languageEnglish
Pages (from-to)31457-31461
Number of pages5
JournalJournal of Biological Chemistry
Volume287
Issue number37
Early online date19 Jul 2012
DOIs
Publication statusPublished - 7 Sept 2012

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