ISSN:
1398-9995
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Defining the structure of the human high-affinity receptor for IgE, FcεRI, is crucial to understand the receptor:ligand interaction, and to develop drugs to prevent IgE-dependent allergic diseases. To this end, a series of four anti-FcεRI monoclonal antibodies (mAbs), including three new mAbs, 47, 54, and 3B4, were used in conjunction with synthetic FcεRI peptides to define functional regions of the Fc IgE-binding site and identify an antagonist of IgE binding. The spatial orientation of the epitopes detected by these antibodies and their relationship to the IgE-binding region of FcεRI was defined by a homology model based on the closely related FcγRIIa. Using recombinant soluble FcεRI-α as well as FcεRI-α expressed on the cell surface, a series of direct and competitive binding experiments indicated that the mAbs detected nonoverlapping epitopes. One antibody (15-1), previously thought to be located close to the IgE-binding site, was precisely mapped to a single loop within the IgE-binding site by both mutagenesis and overlapping synthetic peptides encompassing the entire extracellular domain. A synthetic peptide εRI-11, containing the amino acids 101–120 and the mAb 15-1 epitope, inhibited IgE binding and may form the basis for the development of a useful receptor-based therapy.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1034/j.1398-9995.2000.00485.x
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