HUMAN MONOCLONAL IGE-BINDING FACTORS

在本申请中提出的研究的目的是表征 大鼠和人的IgE结合因子，并阐明其作用机制 它们作用于目标细胞。T细胞杂交瘤将被用作来源 免疫球蛋白结合因子和B细胞杂交瘤将作为靶细胞。 免疫球蛋白结合因子是一类具有亲和力的T细胞因子 伊格。其中一种免疫球蛋白结合因子选择性增强免疫球蛋白反应 (免疫球蛋白增强因子)，而另一种则抑制免疫球蛋白E反应 (免疫球蛋白抑制因子)。大鼠T细胞产生的免疫球蛋白结合因子 杂交瘤与大鼠体内存在的FcEpsilon受体的抗原性相关 B和T淋巴细胞。 在目前的研究方案中，对啮齿动物IgE结合因子的研究将 通过建立和刻画人的特征而扩展到人的系统 能产生IgE结合因子的T细胞杂交瘤。一组 将建立抗人FcEpsilon的单抗 他们中的一些人将与人IgE结合发生交叉反应的预期 各种因素。这些抗体将被用来开发放射免疫分析方法 人Ig E抑制因子和Ig E增强因子。大鼠免疫球蛋白E结合 现有的大鼠T细胞杂交瘤的因子将被用来阐明 Ig E结合因子的效应功能。表面IgE+，胞浆 将建立小鼠免疫球蛋白B细胞杂交瘤，并观察其可能的作用。 这些细胞上的免疫球蛋白结合因子将被研究。小鼠将被注射 用杂交瘤来源的免疫球蛋白E抑制因子检测其体内 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出独特的 控制特应性患者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.