Publications & Reports

Monoclonal antibodies and synthetic peptides define the active site of FcepsilonRI and a potential receptor antagonist.

Rigby LJ, Trist H, Snider J, Hulett MD, Hogarth PM, Rigby LJ, Epa VC
Helen M. Schutt Laboratory for Immunology, Austin Research Institute, Austin Repatriation Medical Centre, Heidelberg, Victoria, Australia.


Defining the structure of the human high-affinity receptor for IgE, Fc,RI, 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-FcepsilonRI monoclonal antibodies (mAbs), including three new mAbs, 47, 54, and 3B4, were used in conjunction with synthetic FcepsilonRI 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 FcepsilonRI was defined by a homology model based on the closely related FcepsilonRIIa. Using recombinant soluble FcRI-alpha as well as FcepsilonRI-alpha 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 epsilonRI-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.


  • Journal: Allergy
  • Published: 01/07/2000
  • Volume: 55
  • Issue: 7
  • Pagination: 609-619