ACCESSORY MECHANISMS IN HUMAN LYMPHOCYTE ACTIVATION

本提案的总体目标是研究辅助功能 参与人类淋巴细胞活化、抗原识别和 免疫调节。这些研究的方向将集中在三个方面 辅助功能的不同而又相互关联的方面。第一，学习 白介素1(IL-1)或白细胞的免疫生物学 热原(LP)将通过研究更精确的方法来扩展 确定IL-1/LP的结构和功能。潜在的临床应用 这项工作的相关性是深远的，因为免疫生理学反应 发烧可能与这些发现有关。第二，体外实验 利用胰岛素来源T细胞识别人类T细胞抗原的模型 胰岛素依赖型糖尿病(IDDM)患者的反应物 将会建立起来。我们期待着这些细胞在体外的发展 IDDM患者胰岛素特异性T细胞克隆或T-T杂交瘤 其T细胞对胰岛素反应强烈。T细胞克隆或T-T 杂交瘤将被用来精确和准确地确定贡献 人类的特定抗原表位呈递。临床部 该项目的相关性与胰岛素的鉴定有关 反应物与抗原特异性免疫生物学系列研究 IDDM患者的抑制性T细胞。此外，这种方法还可以 产生关于抗原特异性的重要的临床有用信息 耐受性，因此使用改变的胰岛素片段进行潜在的免疫治疗 可能导致减少并发症(T细胞反应性、抗体 形成)，同时保持荷尔蒙的作用。最后，配饰 将研究人内皮细胞(EC)的功能，以便 了解潜在的EC-T细胞在体外的相互作用可能是 已实现。这些研究对脉管炎患者的意义 是不言而喻的，这些体外EC-T细胞模型可能提供一种手段 调节血管炎的免疫反应。

The overall aim of this proposal is to investigate the accessory functions involved in human lymphocyte activation, antigen recognition and immunoregulation. The direction of these studies will be focused on three distinct, yet related, aspects of accessory function. First, studies initiated on the immunobiology of Interleukin-1 (IL-1) or leukocytic pyrogen (LP) will be extended by investigating ways to more precisely identify the structure and function of IL-1/LP. The potential clinical relevance of this work is profound in that the immunophysiologic responses to fever are potentially related to these findings. Second, in vitro models of human T cell antigen recognition utilizing T cells from insulin reactors amongst patients with insulin dependent diabetes mellitus (IDDM) will be established. We anticipate the development of these in vitro insulin specific T cell clones or T-T hybridomas from patients with IDDM whose T cells react vigorously to insulin. The T cell clones or T-T hybridomas will be used to precisely and accurately define the contribution of specific antigenic epitope presentation in humans. The clinical relevance of this project is related to the identification of insulin reactors and the serial study of the immunobiology of antigen specific suppressor T cells in humans with IDDM. In addition, this approach could yield important clinially useful information regarding antigen specific tolerance, so that potentially immunotherapy with altered insulin fragments may lead to abrogation of complications (T cell reactivity, antibody formation) while preserving hormone action. Finally, the accessory functions of human endothelial cells (EC) will be studied so that an understanding of potential EC-T cell intereactions in vitro could be achieved. The implications of these studies for patients with vasculitis is self-evident and these in vitro EC-T cell models may provide a means for modulating immune responsses in vasculitis.