IDIOTYPY AND THE ALLERGIC RESPONSE

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The present proposal is designed to evaluate idiotypic- specific regulation of the allergic response in man. Specifically we wish to determine the spectrum of anti-idiotypic antibodies which develop during the course of hyposensitization treatment in patients who have had anaphylactic reactions to bee venom. To obtain sufficient quantities of purified antibody (idiotype) to investigate the nature of the anti-idiotypic response, we propose to produce monoclonal cell lines using Epstein Barr Virus (EBV) infected peripheral cells. Our strategy would be to develop human monoclonal EBV transformants producing the variety of isotypic anti-PLA antibodies that is IgG, Iga, IgM and possibly IgE. We plan to produce Fab and Fab2 fragments from these antibodies and determine if anti-idiotypic antibodies develop in the serum of patients treated by bee venom hyposensitization injections. Next, of importance, would be to develop human monoclonal IgE producing cell lines. Initially, this will be attempted in cells taken from patients with extremely high gamma E levels which would insure sufficient frequency of IgE precursors in peripheral blood. Secondly, we would produce phospholipase A2-specific IgE producing clones from bee sting allergic individuals by expanding precursor populations through a variety of means, and purifying cells prior to infection with EBV. Two laboratories have already published the existence of IgE transformants. Lastly, we will determine if there are common cross reacting idiotypes in anti-PLA antibodies obtained from the same and different individuals and whether these anti-idiotypic antibodies react with anti-PLA antibodies of different isotypes in the same fashion. Monoclonal human IgG has already been isolated from an EBV transformant and it will be used to study the biologic interactions of IgG4 and IgE and the human basophil.