The purpose of the research proposed in this application is to characterize rat and human IgE-binding factors and to elucidate the mechanisms by which they act on target cells. T cell hybridomas will be used as a source of IgE-binding factors and B cell hybridomas will be used as target cells. IgE-binding factors are a family of T cell factors having affinity for IgE. One of the IgE-binding factors selectively enhances the IgE response (IgE-potentiating factor) whereas another suppresses the IgE response (IgE-suppressive factor). IgE-binding factors produced by rat T cell hybridomas are antigenically related for FcEpsilon receptors present on rat B and T lymphocytes. In the present research proposal, studies on rodent IgE-binding factor will be extended into the human system by establishing and characterizing human T cell hybridomas which can make IgE-binding factors. A panel of monoclonal antibodies against the human FcEpsilon will be established with the expectation that some of them will cross-react with human IgE-binding factors. These antibodies will be used to develop radioimmunoassays for human IgE-suppressive factor and IgE-potentiating factor. Rat IgE-binding factors from existing rat T cell hybridomas will be used to elucidate the effector function of IgE-binding factors. Surface IgE+, cytoplasmic IgE-mouse B cell hybridomas will be established and the possible effects of IgE-binding factors on these cells will be studied. Mice will be injected with hybridoma-derived IgE-suppressive factor to determine its in vivo effects on the IgE response. We hope that the research proposed in this application may create unique approaches to control IgE antibody formation in atopic patients.
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