IDIOTYPY AND THE ALLERGIC RESPONSE

本建议旨在评估独特型特异性 调节人类的过敏反应。具体来说，我们希望 确定抗独特型抗体谱， 在脱敏治疗过程中， 对蜂毒有过敏反应的病人 为了获得足够量的纯化抗体（独特型）， 研究抗独特型反应的性质，我们建议 使用Epstein巴尔病毒（EBV）生产单克隆细胞系 感染的外周细胞 我们的策略是开发人类单克隆EB病毒 产生各种同种型抗-PLA的转化体 IgG、伊加、IgM和可能的IgE抗体。 我们计划 从这些抗体产生Fab和Fab 2片段， 确定抗独特型抗体是否在血清中产生， 接受蜂毒脱敏注射的患者。 下一步，重要的是开发人类单克隆IgE 产生细胞系。 最初，这将在细胞中尝试 取自γ-E水平极高的患者， 将确保外周血中IgE前体的足够频率 血 其次，我们将产生磷脂酶A2特异性IgE， 从蜂蜇过敏个体中产生克隆， 前体种群通过各种手段， 在感染EBV之前的细胞。 两个实验室已经 发表了IgE转化体的存在。 最后，我们将确定是否有共同的交叉反应， 获得的抗PLA抗体中的独特型， 不同的个体以及这些抗独特型抗体 在相同条件下与不同同种型的抗PLA抗体反应， 时尚. 单克隆人IgG已经从EBV中分离出来， 它将被用于研究生物相互作用 IgG 4和IgE以及人类嗜碱性粒细胞。

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.