HUMAN MONOCLONAL IGE-BINDING FACTORS

本申请中提出的研究目的是表征 大鼠和人IgE结合因子，并阐明其机制， 作用于靶细胞。 T细胞杂交瘤将被用作 IgE结合因子和B细胞杂交瘤将用作靶细胞。 IgE-结合因子是具有亲和力的T细胞因子家族， IgE。 IgE结合因子之一选择性增强IgE反应 （IgE增强因子），而另一种抑制IgE反应 （IgE抑制因子）。 大鼠T细胞产生的IgE结合因子 杂交瘤与存在于大鼠上Fc ε受体抗原相关 B和T淋巴细胞。 在本研究计划中，啮齿动物IgE结合因子的研究将 通过建立和表征人类， 可以产生IgE结合因子的T细胞杂交瘤。 一组 针对人Fc ε蛋白的单克隆抗体将用 预期其中一些将与人IgE结合交叉反应， 因素 这些抗体将用于开发放射免疫测定， 人IgE抑制因子和IgE增强因子。 大鼠IgE结合 来自现有大鼠T细胞杂交瘤的因子将用于阐明 IgE结合因子的效应子功能。 表面IgE+，细胞质 将建立IgE-小鼠B细胞杂交瘤，并研究 将研究这些细胞上的IgE结合因子。 小鼠将 与杂交瘤衍生的IgE抑制因子，以确定其在体内 对IgE反应的影响 我们希望这项申请中提出的研究可以创造独特的 控制特应性患者中IgE抗体形成的方法。

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.