Project I: This proposal extends the initial evaluation of polymerized antigens to all applicable pollen allergens and initiates studies on dust and mold allergens. Our preliminary studies of polymerized antigen E have provided evidence of greater safety using the same antigenic dose as monomer which will result in fewer injections of allergen and a considerable improvement in cost-benefit ratio for patients. Project II: Studies in this laboratory have demonstrated that we can measure in vitro production of IgE using peripheral blood lymphocytes of patients with hyperimmunoglobulinemia E. The sensitivity of the radioimmunoassay for IgE has been increased. We now propose further studies of IgE production of cells of both allergic and normal individuals and of regulatory mechanisms involved in the production of this immunoglobulin important in allergic disease. Project III: We have found an interesting model of a human disease in an industrial setting induced by inhalation of trimellitic anhydride which combines rapidly with human proteins to form a hapten-protein complex. We have initially characterized IgE mediated reactivity to this hapten. We plan to study IgE, IgG and lymphocyte reactivity directed against this hapten and to correlate the results with the kind and extent of symptoms produced under controlled conditions. Project IV: This project continues studies of the mechanisms of histamine release from allergic basophils. The ability to characterize the biochemical events in the intracellular or cell membrane activated processes provides a potential for pharmacologic inhibition of these processes. Investigators in our laboratory have recently developed the methodology to measure IgE antibodies against ragweed antigen E on the cell membranes of basophils. This permits us to follow seasonal variations of this parameter in the ragweed allergic subject and to study the effect of specific immunotherapy on this determinant of basophil reactivity.