The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells
The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells
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DOI：
10.1083/jcb.200809136
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发表时间：
2009-05-04
影响因子：
7.8
通讯作者：
Vale, Ronald D.
中科院分区：
文献类型：
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作者：
Kaizuka, Yoshihisa;Douglass, Adam D.;Vale, Ronald D.
T细胞和抗原呈递细胞（APC）之间的相互作用可以触发导致T细胞活化的信号传导反应。先前的研究已经表明，T细胞受体（TCR）的连接触发信号级联，其通过TCR和各种信号分子（例如，激酶Lck和接头蛋白LAT [T细胞活化的接头]）进入质膜上的微区。在这项研究中，我们研究了另一种配体-受体相互作用（CD 58-CD 2），该相互作用使用由Jurkat T细胞与模拟APC的平面脂质双层相互作用组成的模型系统来促进T细胞活化。我们发现，在没有TCR活化的情况下，CD 58与CD 2的结合也通过信号分子（包括TCR-zeta链、Lck和LAT）的肌动蛋白依赖性聚结（coalescence）到微结构域中来诱导信号传导。当同时激活时，TCR和CD 2最初共定位在小的微区中，但随后分成单独的区域;这种空间分离可能使两种受体能够协同增强信号传导。我们的研究结果表明，两种结构不同的受体都诱导质膜中分子的快速空间重组，这表明信号分子浓度的局部增加如何触发T细胞信号传导的模型。
The interaction between a T cell and an antigen-presenting cell (APC) can trigger a signaling response that leads to T cell activation. Prior studies have shown that ligation of the T cell receptor (TCR) triggers a signaling cascade that proceeds through the coalescence of TCR and various signaling molecules (e.g., the kinase Lck and adaptor protein LAT [linker for T cell activation]) into microdomains on the plasma membrane. In this study, we investigated another ligand-receptor interaction (CD58-CD2) that facilities T cell activation using a model system consisting of Jurkat T cells interacting with a planar lipid bilayer that mimics an APC. We show that the binding of CD58 to CD2, in the absence of TCR activation, also induces signaling through the actin-dependent coalescence of signaling molecules (including TCR-zeta chain, Lck, and LAT) into microdomains. When simultaneously activated, TCR and CD2 initially colocalize in small microdomains but then partition into separate zones; this spatial segregation may enable the two receptors to enhance signaling synergistically. Our results show that two structurally distinct receptors both induce a rapid spatial reorganization of molecules in the plasma membrane, suggesting a model for how local increases in the concentration of signaling molecules can trigger T cell signaling.