Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores.
Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores.
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DOI：
10.1084/jem.161.3.446
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发表时间：
1985-03-01
期刊：
影响因子：
--
通讯作者：
Stobo JD
中科院分区：
文献类型：
--
作者：
Imboden JB;Stobo JD
针对 T3 抗原受体复合物的抗体可以激活人类 T 细胞系 Jurkat，产生白细胞介素 2 (2-5)。这种激活是由受体介导的游离细胞质钙离子 [Ca2+]i 浓度增加启动的 (3, 4)。在本次交流中，我们研究了受体复合物增加 Jurkat 细胞中 [Ca2+ )i 的机制。当细胞外 Ca2+ 被 EGTA 耗尽时，[Ca2+]i 会发生初始受体介导的变化。因此，T 细胞抗原受体的扰动会产生一个信号，从细胞内储存中调动 Ca2+。由于肌醇三磷酸似乎充当某些激素受体的信号，因此我们测量了 Jurkat 中肌醇三磷酸和其他肌醇磷酸化合物的水平。针对抗原受体异二聚体或 T3 决定簇的抗体会导致所有三种磷酸肌醇显着升高。肌醇磷酸盐的这些变化并不是继发于受体介导的 [Ca2+]i 增加，正如 Ca2+ 离子载体离子霉素无法影响任何这些化合物的水平所证明的那样。纯化的三磷酸肌醇的浓度在 0.1 至 1 µM 之间，可从透化的 Jurkat 细胞中释放 Ca2+。总而言之，这些数据表明，在激活过程中，T3 抗原受体复合物的扰动会产生肌醇三磷酸。该化合物充当细胞内信号，从细胞内储存中释放 Ca2+，导致 [Ca2+]i 增加。
Antibodies against the T3-antigen receptor complex can activate the human T cell line, Jurkat, to produce interleukin 2 (2-5). This activation is initiated by a receptor-mediated increase in the concentration of free cytoplasmic calcium ions [Ca2+]i (3, 4). In this communication, we investigate the mechanism by which the receptor complex increases [Ca2+ )i in Jurkat cells. The initial receptor- mediated change in [Ca2+]i can occur when extracellular Ca2+ is depleted by EGTA. Perturbation of the T cell antigen receptor, therefore, generates a signal which mobilizes Ca2+ from intracellular stores. As inositol trisphosphate appears to function as such a signal for certain hormone receptors, we measured the levels of inositol trisphosphate and of the other inositol phosphate compounds in Jurkat. Antibodies to either the antigen receptor heterodimer or T3 determinants result in marked elevations of all three inositol phosphates. These changes in inositol phosphates are not secondary to the receptor-mediated increases in [Ca2+]i as demonstrated by the inability of the Ca2+ ionophore, ionomycin, to affect the levels of any of these compounds. In concentrations between 0.1 and 1 microM, purified inositol trisphosphate releases Ca2+ from permeabilized Jurkat cells. Taken together, these data indicate that, during activation, perturbation of the T3-antigen receptor complex generates inositol trisphosphate. This compound functions as an intracellular signal to release Ca2+ from intracellular stores, leading to increases in [Ca2+]i.