IA REACTIVE T CELL CLONES: RECOGNITION AND FUNCTION

同基因或自体混合淋巴细胞反应(SMLR)已经被 定义为T细胞对体外刺激的增殖反应 同基因或自体非T细胞，携带Ia抗原。尽管 SMLR已经得到了很好的表征，它的性质和功能意义 体内的反应性T细胞还没有得到解决。要解决这些问题 我们已经开发出一系列识别自我Ia的T细胞克隆 在没有外来抗原的情况下。这些细胞作为辅助性T细胞在 抗原反应性T细胞和同种异体反应性细胞毒T细胞的增殖 并触发静息B细胞的增殖和分化， 但在初步实验中，似乎不包含抗原反应性T 细胞。基于这些观察，我们希望：1)确定是否 在SMLR中反应的自身反应性T细胞是抗原反应性T细胞 细胞；2)识别自身反应的T细胞标志物，而不是 并制备同种异体反应性T细胞的单抗。 识别自身Ia的T细胞受体的特性；3) 体外分析自身反应性T细胞的免疫调节作用 确定体内耗尽SMLR反应性T细胞对 免疫应答；4)分析正常免疫应答的基础 LYL+2-/L3T4+T细胞转化为自身反应性T细胞。实验已经被 旨在确定低亲和力T细胞受体是否与Ia相互作用 都是触发T细胞所必需的，并分析它们之间的关系 自身反应性T细胞克隆到克隆的抗原特异性T细胞系。 这些实验将利用一系列具有良好特性的自体反应 用于制备T细胞杂交瘤和单抗的T细胞克隆 针对Ia的T细胞受体抗体的最终目标是 T细胞自身Ia受体的特性及其与T细胞受体的关系 抗原特异性T细胞受体。我们最近观察到这是正常的 LYL+2-/L3T4+T细胞对自身反应性T细胞的特异性反应提示 可能有一个自动调节网络和初步实验来 探讨T-T识别的特异性和依据 相互作用的概述。这些实验应该会阐明这种作用 自身反应性T细胞对免疫反应的调节作用 提供有关这些细胞如何参与自身免疫和 肿瘤。

The syngeneic or autologous mixed lymphocyte reaction (SMLR) has been defined as a T cell proliferative response to in vitro stimulation with syngeneic or autologous non-T cells, bearing Ia antigens. Although the SMLR has been well characterized, the nature and functional significance of the responding T cells in vivo has not been resolved. To address these issues we have developed a series of T cell clones which recognize self-Ia in the absence of foreign antigens. These cells serve as helper T cells in the proliferation of antigen reactive T cells and alloreactive cytotoxic T cells and trigger the proliferation and differentiation of resting B cells, but in preliminary experiments do not appear to contain antigen reactive T cells. Based on these observations we wish to : 1) determine if autoreactive T cells which respond in the SMLR are antigen responsive T cells; 2) identify a T cell marker specific for autoreactive but not alloreactive T cells and to prepare monoclonal antibodies for the characterization of the T cell receptor which recognizes self-Ia; 3) analyze the immunoregulatory role of autoreactive T cells in vitro and determine the effects of in vivo depletion of SMLR reactive T cells on the immune response; and 4) analyze the basis of the response of normal Lyl+2-/L3T4+ T cells to autoreactive T cells. Experiments have been designed to determine if low affinity T cell receptor interactions with Ia are essential in the triggering of T cells and to analyze the relationship of autoreactive T cell clones to cloned antigen-specific T cell lines. These experiments will utilize a series of well characterized autoreactive T cell clones for preparation of T cell hybridomas and monoclonal antibodies to the T cell receptor for Ia with the ultimate goal of characterizing the T cell receptor for self-Ia and its relationship to the antigen-specific T cell receptor. Our recent observation that normal Lyl+2-/L3T4+ T cells respond specifically to autoreactive T cells suggests that there may be an autoregulatory network and preliminary experiments to investigate the specificity and basis of recognition of this T-T interaction are outlined. These experiments should shed light on the role of autoreactive T cells on regulation of the immune response and may provide insights as to how these cells participate in autoimmunity and neoplasia.