Calcium dependency of antigen-specific (T3-Ti) and alternative (T11) pathways of human T-cell activation.
Calcium dependency of antigen-specific (T3-Ti) and alternative (T11) pathways of human T-cell activation.
复制标题
人类 T 细胞激活的抗原特异性 (T3-Ti) 和替代 (T11) 途径的钙依赖性。
DOI：
10.1073/pnas.81.21.6836
复制
发表时间：
1984
影响因子：
11.1
通讯作者：
Reinherz,EL
中科院分区：
文献类型：
--
作者：
Weiss,MJ;Daley,JF;Hodgdon,JC;Reinherz,EL
人类T淋巴细胞被两种谱系特异性表面成分激活：抗原/主要组织相容性复合物受体（T3-Ti）和不相关的T11分子。其中任何一种与它们各自的配体相互作用通过依赖白细胞介素2（IL-2）的自分泌机制导致t细胞增殖。为了开始表征激活过程的分子细节，使用人类t细胞克隆和针对其表面成分的单克隆抗体来检查Ca2+的作用。在这里，我们表明，在触发T3-Ti或T11分子的几分钟内，细胞内Ca2+浓度大幅增加，通过quin-2荧光测量。这对于诱导、抑制和细胞毒性克隆中t细胞增殖的诱导是必不可少的，因此可能在自分泌生长途径的早期阶段是必需的。因此，EGTA螯合外源性Ca2+特异性抑制抗t3 - ti或抗t11单克隆抗体触发的增殖，但不影响外源性IL-2触发。此外，Ca2+离子载体A23187本身可以启动克隆增殖。
Human T lymphocytes are activated by two lineage-specific surface components: the antigen/major histocompatibility complex receptor (T3-Ti) and the unrelated T11 molecule. Interaction of either of these with their respective ligands leads to T-cell proliferation via an interleukin 2(IL-2) dependent autocrine mechanism. To begin to characterize the molecular details of the activation process, the role of Ca2+ was examined using human T-cell clones and monoclonal antibodies directed against their surface components. Here, we show that within minutes of triggering either the T3-Ti or T11 molecule, there is a large increase in intracellular Ca2+ concentration, as measured by quin-2 fluorescence. This is essential for induction of T-cell proliferation in inducer, suppressor, and cytotoxic clones and therefore presumably is required at an early step in the autocrine growth pathway. Thus, chelating exogenous Ca2+ with EGTA specifically inhibits proliferation triggered by anti-T3-Ti or anti-T11 monoclonal antibodies, but it does not affect triggering by exogenous IL-2. In addition, the Ca2+ ionophore A23187 can, by itself, initiate clonal proliferation.