IMMUNOREGULATION BY ANTI-IDIOTOPES

这项研究的长期目标是阐明 自身反应性T细胞的生物学功能， 免疫球蛋白分子的独特位（Id）。 这些ID- 特异性T细胞（TID）被认为是免疫调节的主要调节因子。 对细菌抗原的抗体反应，也许， Id阳性淋巴瘤的免疫监视细胞。 的 拟议的项目是由一种新的方法，建立 稳定的T细胞系/克隆，其特异性识别 T15免疫球蛋白的独特位。 T15特异性TID系 使用同基因B细胞淋巴瘤转染 T15基因 由于T15分子是 保护小鼠免受沙门氏菌感染的抗体。肺炎（Pn） 感染，T15特异性TID的可用性开辟了 充分阐明了T15 Id + B细胞对Pn应答的调控。 此外，受体的特异性和性质的自体 现在可以正式研究TID。 第一个目标是确定 TcR结构和TId系/克隆的精细特异性 并阐明这些T细胞对各种形式的 可溶性和细胞结合的Id分子。 二是 通过TId系/克隆调节抗体对Pn的应答 将在体外进行研究，以确定机制， 其中TID刺激和/或抑制Id+的功能， Pn反应性B淋巴细胞。 工业贸易署与 抗原特异性辅助性T细胞克隆在抗体调节中的作用 还将使用淋巴细胞培养物研究反应 用各种形式的Pn抗原免疫。 第三个目标是 使用（a）确定TId在体内的生物学意义 将TId系/克隆过继转移到裸鼠中，（B） 测量正常人中TId的频率和定位 和T15转基因小鼠，和（c）各种TId亚群的缺失， 原位接种，随后进行Pn免疫。 最后一个目的是探索 TId系/克隆的细胞抑制（生长抑制）作用 Id+ B细胞淋巴瘤的体外实验及小鼠抗Id的保护作用 移植的肿瘤

The long-term objective of this research is to elucidate the biological functions of the self-reactive T cells that recognize the idiotopes (Id) of immunoglobulin molecules. These Id- specific T cells (TId) are perceived as the major regulators of antibody response to bacterial antigens and, perhaps, as immunosurveillance cells for the Id-positive lymphomas. The proposed project was fueled by a new method for establishment of stable T cell lines/clones that specifically recognize the idiotopes of the T15 immunoglobulin. The T15-specific TId lines have been derived using syngeneic B cell lymphoma transfected with the T15 genes. Since the T15 molecule is the prototype of the antibody that protects mice against S. pneumonial (Pn) infection, the availability of T15-specific TId opens the way to fully elucidate the regulation of T15Id + B cell response to Pn. Moreover, the receptor specificity and properties of autologous TId can now be formally studied. The first aim is to determine the TcR structure and the fine specificity of TId lines/clones and to elucidate the response of these T cells to various forms of Id molecules, both soluble and cell-bound. Secondly, the regulation of antibody response to Pn by the TId lines/clones will be studied in vitro, in order to determine the mechanisms by which the TId stimulate and/or suppress the functions of the Id+, Pn-responsive B lymphocytes. The collaboration of TId, with antigen-specific T helper clones in regulation of antibody response will also be studied, using lymphocyte cultures immunized with various forms of the Pn antigen. The third aim is to determine the biological significance of TId in vivo using (a) adoptive transfer of TId lines/clones into nude mice, (b) measurements of the frequency and localization of TId in normal and T15-transgenic mice, and (c) deletion of various TId subsets, in situ, followed by Pn immunization. The last aim is to explore the cytostatic (growth-inhibitory) effects of TId lines/clones on Id+ B cell lymphomas in vitro and the protection of mice against the transplanted tumors.