Stimulation strength controls the rate of initiation but not the molecular organisation of TCR-induced signalling
Stimulation strength controls the rate of initiation but not the molecular organisation of TCR-induced signalling
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DOI：
10.7554/elife.53948
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发表时间：
2020-05-15
期刊：
影响因子：
7.7
通讯作者：
Richard, Arianne C.
中科院分区：
文献类型：
--
作者：
Ma, Claire Y.;Marioni, John C.;Richard, Arianne C.
数百万具有不同TCR的初始T细胞可以与肽-MHC配体相互作用，但很少会激活。值得注意的是，这种精细的控制是使用有限的细胞内机制来协调的。目前尚不清楚刺激强度的变化是否会改变导致T细胞活化的信号事件的程序。使用质谱流式细胞术同时测量小鼠CD 8（+）T细胞活化过程中的多种信号传导途径，我们发现了一个共享的远端信号传导事件程序，无论TCR刺激的强度如何。此外，早期反应基因Nr 4a 1和Irf 8的转录和核糖体蛋白S6的激活之间的关系也是保守的刺激。相反，我们发现刺激强度决定了细胞通过该网络启动信号的速率。这些数据表明，TCR诱导的信号传导导致协调的激活程序，通过刺激强度调节速率但不调节组织。
Millions of naive T cells with different TCRs may interact with a peptide-MHC ligand, but very few will activate. Remarkably, this fine control is orchestrated using a limited set of intracellular machinery. It remains unclear whether changes in stimulation strength alter the programme of signalling events leading to T cell activation. Using mass cytometry to simultaneously measure multiple signalling pathways during activation of murine CD8(+) T cells, we found a programme of distal signalling events that is shared, regardless of the strength of TCR stimulation. Moreover, the relationship between transcription of early response genes Nr4a1 and Irf8 and activation of the ribosomal protein S6 is also conserved across stimuli. Instead, we found that stimulation strength dictates the rate with which cells initiate signalling through this network. These data suggest that TCR-induced signalling results in a coordinated activation program, modulated in rate but not organization by stimulation strength.