title: Mapping of the CD23 binding site on immunoglobulin E (IgE) and allosteric control of the IgE-Fc epsilonRI interaction.
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, FcεRI on mast cells and basophils and CD23 on B cells. IgE cross-linked by allergen triggers mast cell activation via FcεRI, 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 FcεRI interaction sites are at opposite ends of the Cε3 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 FcεRI 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-FcεRI and IgE-CD23 interactions.
authors: Randall Division of Cell and Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, United Kingdom.
authors: Susmita
authors: S
authors: Borthakur
authors: Richard G
authors: RG
authors: Hibbert
authors: Marie O Y
authors: MO
authors: Pang
authors: Norhakim
authors: N
authors: Yahya
authors: Heather J
authors: HJ
authors: Bax
authors: Michael W
authors: MW
authors: Kao
authors: Alison M
authors: AM
authors: Cooper
authors: Andrew J
authors: AJ
authors: Beavil
authors: Brian J
authors: BJ
authors: Sutton
authors: Hannah J
authors: HJ
authors: Gould
authors: James M
authors: JM
authors: McDonnell
mesh_terms: D000494:Allosteric Regulation / Q000276:immunology; D001491:Basophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010449:Peptide Mapping / Q000379:methods; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D017455:Receptors, IgE; D007073:Immunoglobulin E