SOLUBLE HUMAN HIGH-AFFINITY RECEPTOR FOR IGE ABROGATES THE IGE-MEDIATED ALLERGIC REACTION

The high-affinity receptor for IgE (FcepsilonRI) has a tetrameric structure composed of one alpha, one beta, and two disulfide-linked gamma subunits, of which the alpha subunit binds IgE with high affinity. A recombinant soluble form of the ectodomain of the human FcepsilonRIalpha subunit (rsFcepsilonRIalpha) was recently generated by gene engineering and was verified to bind IgE with an affinity as high as that of native FcepsilonRI on the cell surface. rsFcepsilonRIalpha was prepared on a large scale in order to analyze its biological function. rsFcepsilonRIalpha completely inhibited IgE binding to the cell surface, resulting in abrogation of the chemical mediator release from RBL-2H3 cells. Furthermore it completely abolished the passive cutaneous anaphylaxis (PCA) response by trapping IgE specifically when it was administered into rats prior to IgE sensitization. Even after IgE sensitization, treatment of rsFcepsilonRIalpha substantially reduced the PCA response. It was finally shown that rsFcepsilonRIalpha inhibited IgE binding to human peripheral blood basophils and the histamine release from them. In this paper we address the ability of rsFcepsilonRIalpha to specifically prevent the IgE-mediated allergic reaction.