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, 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. 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?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.

SUBMITTER: Borthakur S 

PROVIDER: S-EPMC3438978 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature