REGULATION OF REAGINIC ANTIBODY RESPONSE

本研究的目的是寻找抑制免疫球蛋白E的策略 以抗原特异的方式对过敏原的抗体反应。上一首 研究表明，一种脂调节素样淋巴因子，即糖基化 抑制因子(GIF)，促进抗原特异性的产生 抑制性T细胞(T细胞)，形成自己的GIF。关于抗原性 在刺激下，抗原特异的TS形成GIF，与名义上的 抗原。与抗原结合的GIF似乎与抗原- 特异性TS因子(TSF)，由抗原结合链和 非特定GIF。根据这些发现，我们建立了一种免疫学 用抗原免疫的小鼠脾构建TS杂交瘤的方法 细胞，并证明了杂交瘤的抗原结合GIF 抑制脾细胞供者的抗体反应 同源抗原。将相同的方法应用于 一名对蜂毒过敏的患者的外周血单核细胞，我们 已建立的产生抗原结合GIF的人T细胞杂交瘤 CD3在细胞上的交联性。由于小鼠GIF被分离出来 生化同质性，i)将尝试分离人类 非特异性GIF，并对其抗原结合性GIF进行生化表征 两个物种都是。Ii)基于小鼠非特异性GIF、CDNA的结构 编码淋巴因子的克隆将被分离，实验将被 扩增获得编码人GIF的CDNA。Iii)我们将测试 假设抗原结合的GIF以及细胞的T细胞受体 该因子来源识别代表外源基因的公共表位 抗原分子中的结构，以及一定的表位特异性 淋巴因子对免疫抑制作用是必不可少的。四) 最后，GIF的免疫抑制机制将在 小鼠系统。因为我们最近的研究表明，GIF抑制了 脾贴壁细胞提呈抗原对T细胞的影响 将分析抗原提呈细胞上的抗原结合GIF。

The purpose of this research is to find some maneuvers to suppress the IgE antibody response to allergen in an antigen-specific manner. Previous studies have shown that a lipomodulin-like lymphokine, i.e., glycosylation inhibiting factor (GIF), facilitated the generation of antigen-specific suppressor T cells (Ts), which form their own GIF. Upon antigenic stimulation, the antigen-specific Ts form GIF that has affinity for nominal antigen. The antigen-binding GIF appears to be identical to antigen- specific Ts factor (TsF), and composed of antigen-binding chain and nonspecific GIF. Based on the findings, we established an immmunological maneuver to construct Ts hybridomas from antigen-primed murine spleen cells, and demonstrated that antigen-binding GIF from the hybridomas suppressed the antibody response of the donor of the spleen cells to homologous antigen. As the results of application of the same method to peripheral blood mononuclear cells of a patient, allergic to bee venom, we established human T cell hybridomas which produce antigen-binding GIF upon cross-linking of CD3 on the cells. Since murine GIF was isolated to biochemical homogeneity, i) attempts will be made to isolate human nonspecific GIF, and to biochemically characterize antigen-binding GIF of both species. ii) Based on the structure of murine nonspecific GIF, CDNA clone encoding the lymphokine will be isolated, and the experiments will be extended to obtain CDNA encoding human GIF. iii) We shall test the hypothesis that antigen-binding GIF as well as T cell receptors of the cell source of the factor recognize a common epitope representing an external structure in the antigen molecule, and that a certain epitope specificity of the lymphokine is essential for immunosuppressive effects. iv) Finally, mechanisms of immunosuppression by GIF will be investigated in murine system. Since our recent studies indicated that GIF suppresses presentation of antigen by splenic adherent cells to T cells, the effect of antigen-binding GIF on antigen-presenting cells will be analyzed.