ANTIGEN RECOGNITION BY HELPER T-CELLS ELICITS A SEQUENCE OF DISTINCT CHANGES OF THEIR SHAPE AND INTRACELLULAR CALCIUM
ANTIGEN RECOGNITION BY HELPER T-CELLS ELICITS A SEQUENCE OF DISTINCT CHANGES OF THEIR SHAPE AND INTRACELLULAR CALCIUM
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DOI：
10.1016/s0960-9822(00)00130-5
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发表时间：
1994-07-01
期刊：
影响因子：
9.2
通讯作者：
TRAUTMANN, A
中科院分区：
文献类型：
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作者：
DONNADIEU, E;BISMUTH, C;TRAUTMANN, A
背景：当T细胞受体复合体识别与抗原提呈细胞表面的MHC II类分子相关的抗原片段时，辅助性T细胞激活在体内启动。在以前对这种现象的大多数研究中，T细胞不是用抗原提呈细胞刺激的，而是用CD3特异性抗体刺激的。这一方法提供了对T细胞受体刺激所触发的一连串分子事件的相当多的了解。然而，细胞间相互作用的具体后果仍然知之甚少。因此，我们使用了一种同时提供传输和荧光图像的双重成像系统来研究人类CD4(+)抗原特异性T细胞克隆对转II类抗原的小鼠成纤维细胞递呈抗原的形态变化和细胞内钙离子浓度([Ca2+](I))的变化。结果：负载钙敏感荧光染料Fura-2的T细胞在与抗原冲击的抗原提呈细胞单层接触后，被单独监测了半小时。人们发现，这种反应有三个不同的阶段。在接触后的最初几分钟里，T细胞在抗原提呈细胞上移动，就像是在扫描它们。几分钟后，一个振荡的[Ca~(2+)](I)反应开始，伴随着细胞的固定和伪足的收缩。这种舍入可能是依赖于钙离子的，因为它也可以被离子霉素或thapsigargin触发。在[Ca~(2+)](I)反应的后期，T细胞变得扁平并进一步延长，提示与抗原提呈细胞的粘附性增加。结论：T细胞激活的生理信号，即抗原识别，是一个三步过程，使人想起以前观察到的中性粒细胞与内皮细胞相互作用的三个步骤。在这些连续的步骤中，一个流动的、弱相互作用的T细胞被转化为一个完全参与激活途径的静止细胞。因此，抗原识别不是瞬间的，而是通过逐渐放大少数抗原分子提供的信号来缓慢进化，最终导致T细胞激活。
Background: Helper T-cell activation is initiated in vivo when the T-cell receptor complex recognizes an antigen fragment associated with MHC class II molecules on the surface of an antigen-presenting cell. In most previous studies of this phenomenon, T cells were stimulated not with antigen-presenting cells, but with CD3-specific antibodies. This approach provided considerable understanding of the cascade of molecular events triggered by T-cell receptor stimulation. However, the specific consequences of cell-cell interactions are still poorly understood. We therefore used a dual imaging system that provides simultaneous transmission and fluorescence images to study the morphological changes and variations of intracellular calcium concentration ([Ca2+](i)) triggered in a human CD4(+) antigen-specific T-cell clone in response to antigen presented by a class II-transfected murine fibroblast.Results: T cells loaded with the Ca2+-sensitive fluorescent dye Fura-2 were individually monitored for half an hour following their contact with a monolayer of antigen-pulsed antigen-presenting cells. The response was found to have three distinct phases. During the first few minutes after contact, the T cell moves over the antigen-presenting cells, as if 'scanning' them. After several minutes, an oscillating [Ca2+](i) response begins, accompanied by the immobilization of the cell and the retraction of pseudopodia. This rounding-up was probably Ca2+-dependent, as it could also be triggered by ionomycin or thapsigargin. Later during the [Ca2+](i) response, the T cell becomes flattened and further elongated, suggesting increased adhesion to antigen-presenting cells.Conclusions: The physiological signal for T-cell activation, antigen recognition, is a three-step process reminiscent of the three steps previously observed in the interaction between neutrophils and endothelial cells. During these successive steps, a mobile, weakly interacting T cell is transformed into an immobile cell fully engaged in the activation pathway. Thus, antigenic recognition is not instantaneous, but evolves slowly by progressive amplification of the signal given by a few antigen molecules, eventually resulting in T-cell activation.