Three-dimensional segregation of supramolecular activation clusters in T cells
Three-dimensional segregation of supramolecular activation clusters in T cells
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DOI：
10.1038/25764
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发表时间：
1998-09-03
期刊：
影响因子：
64.8
通讯作者：
Kupfer, A
中科院分区：
文献类型：
--
作者：
Monks, CRF;Freiberg, BA;Kupfer, A
抗原呈递细胞 (APC) 对 T 细胞的激活取决于多个抗原受体传递的信号的复杂整合。 T 细胞 (1,2) 中的大多数受体近端激活事件均使用多价抗受体抗体进行鉴定，从而无需使用更复杂的 APC。由于 APC 中的生理膜相关配体和激活抗体可能触发相同的生化途径，因此尚不清楚为什么抗体即使在饱和浓度下也无法触发一些生理 T 细胞反应 (3)。在这里，我们在单细胞水平上研究 T 细胞对天然配体的反应。我们使用数字成像系统，分析了抗原特异性相互作用期间聚集在 T 细胞和 APC 接触处的受体和细胞内蛋白质的三维分布 (3,4)。令人惊讶的是，这些蛋白质没有表现出均匀的寡聚化，而是在细胞接触内聚集成分离的三维结构域。这些新的、空间分离的超分子激活簇的抗原特异性形成可能会产生适当的生理反应，并可能解释 T 细胞对抗原的高敏感性。
Activation of T cells by antigen-presenting Cells (APCs) depends on the complex integration of signals that are delivered by multiple antigen receptors. Most receptor-proximal activation events in T cells(1,2) were identified using multivalent anti-receptor antibodies, eliminating the need to use the more complex APCs. As the physiological membrane-associated ligands ori the APC and the activating antibodies probably trigger the same biochemical pathways, it is unknown why the antibodies, even at saturating concentrations, fail to trigger some of the physiological T-cell responses(3). Here we study, at the level of the single cell, the responses of T cells to native ligands. We used a digital imaging system and analysed the three-dimensional distribution of receptors and intracellular proteins that cluster at the contacts between T cells and APCs during antigen-specific interactions(3,4). Surprisingly, instead of showing uniform oligomerization, these proteins clustered into segregated three-dimensional domains within the cell contacts. The antigen-specific formation of these new, spatially segregated supramolecular activation clusters may generate appropriate physiological responses and may explain the high sensitivity of the T cells to antigen.