Monks C R, Freiberg B A, Kupfer H, Sciaky N, Kupfer A
Division of Basic Science, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Nature. 1998 Sep 3;395(6697):82-6. doi: 10.1038/25764.
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 were identified using multivalent anti-receptor antibodies, eliminating the need to use the more complex APCs. As the physiological membrane-associated ligands on 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. 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. 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.
抗原呈递细胞（APC）激活T细胞依赖于多种抗原受体传递信号的复杂整合。T细胞中大多数受体近端激活事件是使用多价抗受体抗体鉴定出来的，从而无需使用更为复杂的APC。由于APC上的生理性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即使在饱和浓度下，抗体仍无法触发某些生理性T细胞反应。在此，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T细胞与APC接触处聚集的受体和细胞内蛋白的三维分布。令人惊讶的是，这些蛋白并未呈现均匀的寡聚化，而是在细胞接触区域内聚集成分离的三维结构域。这些新的、空间上分离的超分子激活簇的抗原特异性形成可能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。
