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 language | English |
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Pages (from-to) | 31457-31461 |
Number of pages | 5 |
Journal | Journal of Biological Chemistry |
Volume | 287 |
Issue number | 37 |
Early online date | 19 Jul 2012 |
DOIs | |
Publication status | Published - 7 Sept 2012 |