IDIOTYPY AND THE ALLERGIC RESPONSE

本提案旨在评估独特型特有 人体过敏反应的调节。具体来说，我们希望 测定抗独特型抗体的谱 在减敏治疗过程中的发展 对蜂毒有过敏反应的病人。 获得足够数量的纯化抗体(独特型)以 研究抗独特型反应的性质，我们建议 用EB病毒(EBV)制备单克隆细胞系 感染的外周细胞。 我们的战略将是开发人类单克隆性EBV 产生多种同型抗磷脂酶A的转化子 抗体，即免疫球蛋白、免疫球蛋白、免疫球蛋白M，可能还有免疫球蛋白E。我们计划 从这些抗体中产生Fab和Fab2片段 确定抗独特型抗体是否在患者的血清中产生 蜂毒减敏注射治疗3例。 下一步，重要的是开发人的单抗IgE 生产细胞系。最初，将在单元格中尝试此操作 取自伽马E水平极高的患者 会确保外周血中有足够的IgE前体 血。其次，我们将生产磷脂酶A2特异性的IgE 通过扩增产生蜜蜂叮咬过敏个体的克隆 通过各种手段，对前体种群进行提纯 EBV感染前的细胞。已经有两个实验室 发表了IgE转化子的存在。 最后，我们将确定是否存在共同的交叉反应 从同一来源和同一来源获得的抗解放军抗体的独特型 以及这些抗独特型抗体 与不同同种类型的抗解放军抗体在同一 时尚。 已从一种EB病毒中分离出单克隆人免疫球蛋白 转化子，并用于研究生物相互作用 免疫球蛋白G4、免疫球蛋白E和人类嗜碱性粒细胞。

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.