REGULATION OF T LYMPHOCYTE IMMUNE RESPONSES

T淋巴细胞在细胞和体液中都发挥着不可或缺的作用 免疫反应，执行直接效应功能，如 细胞溶解以及通过分泌的 淋巴因子。T细胞的特殊功能被确定 通过独立于 获得特异性抗原受体(TCR)。TCR 解释了T细胞反应的特异性。然而，有几个 由单抗定义的其他T细胞表面分子 (单抗)，也影响T细胞的反应。其中包括CD4， 人T细胞表达CD8、LFA-1(和 小鼠T细胞上L3T4、Lyt-2、3和LFA-1的相应结构 细胞和CD3和CD2(小鼠的同类细胞没有 已被确定)。T细胞的反应也是 白介素2(IL-2)对T细胞的影响 增殖，但这也导致克隆的小鼠HTL成为 对抗原无反应。拟议的研究涉及以下方面 与T细胞激活相关的事件，与 T细胞对抗原无反应性的研究进展 刺激和发展更好的监管方法 体内的免疫反应。具体地说，我们打算推导出mAb 与T细胞中重要的细胞表面结构发生反应 激活包括人CD3和人CD3的小鼠同源物 CD2分子复合体；确定T细胞表面的连接 具有特殊功能的结构通过构建“细胞溶解- 使用药物标记的克隆小鼠CTL和 HTL作为聚变合作伙伴；以确定 IL-1诱导克隆性小鼠HTL的无反应 2或暴露于高水平的抗原；以区分 通过TCR发起的蜂窝事件(导致 淋巴因子的产生)和通过IL-2启动的 受体(导致增殖)，并比较IL-2- CTL的依赖和IL-2非依赖的增殖途径 通过在HTL中发现的自分泌途径来确定 允许持续复制的“附属细胞”的特性 克隆的小鼠T细胞；开发额外的抗TCR单抗 为了确定T细胞独特型在免疫中的作用 调节；确定实现的最佳方法 针对T细胞的单抗在体内的免疫抑制作用 表面结构；并确定其功能意义 同种异体移植物增强中单抗同种异型。

T lymphocytes play an integral role in both cellular and humoral immune responses, carrying out direct effector functions such as cytolysis as well as mediating regulatory functions via secreted lymphokines. The particular functions of T cells are determined by differentiation events that occur independently of the acquisition of the specific receptor for antigen (TCR). The TCR accounts for the specificity of T cell responses. However, several other T cell surface molecules, defined by monoclonal antibodies (mAb), also affect the response of the T cell. These include CD4, CD8, and LFA-1 expressed by human T cells (and the corresponding structures, L3T4, Lyt-2,3, and LFA-1 on murine T cells and CD3 and CD2 (for which murine counterparts have not been identified with certainty). The responses of T cells also are influenced by interleukin 2 (IL-2) which induces T cell proliferation but which also causes cloned murine HTL to become unresponsive to antigen. The proposed studies are concerned with events associated with T cell activation, events associated with development of unresponsiveness of T cells to antigenic stimulation, and development of better approaches to regulate immune responses in vivo. Specifically, we intend to derive mAb reactive with cell surface structures that are important in T cell activation including the murine homologues of human CD3 and the CD2 molecular complex; to determine linkage of T cell surface structures with particular functions by constructing "cytolytic- helper" T cell hybrids using drug-marked cloned murine CTL and HTL as fusion partners; to determine the basis for unresponsiveness induced in cloned murine HTL by exposure to IL- 2 or by exposure to high levels of antigen; to distinguish between cellular events initiated through the TCR (leading to lymphokine production) and those initiated through the IL-2 receptor (leading to proliferation), and to compare the IL-2- dependent and IL-2-independent pathways of proliferation in CTL with the autocrine pathway found in HTL; to determine the properties of "accessory cells" that permit continued replication of cloned murine T cells; to develop additional anti-TCR mAb in order to determine the role of T cell idiotype in immune regulation; to determine the optimal method to achieve immunosuppression in vivo using mAb directed against T cell surface structures; and to determine the functional significance of mAb isotype in allograft enhancement.