학술논문
Mapping of the CD23 Binding Site on Immunoglobulin E (IgE) and Allosteric Control of the IgE-Fc∈RI Interaction.
Document Type
Article
Author
Source
Subject
*IMMUNOGLOBULIN E
*GENE mapping
*CD23 antigen
*ALLOSTERIC regulation
*NUCLEAR magnetic resonance
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Language
ISSN
0021-9258
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∈RI on mast cells and basophils and CD23 on B cells. IgE cross-linked by allergen triggers mast cell activation via Fc∈RI, whereas IgE-CD23 interactions control IgE expression levels.Wehave 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∈RI interaction sites are at opposite ends of the C∈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∈ 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∈RI and IgE-CD23 interactions. [ABSTRACT FROM AUTHOR]