Mechanobiological Control of the Immune Response
Mechanobiological Control of the Immune Response
复制标题
免疫反应的机械生物学控制
DOI：
10.1016/j.bpj.2018.11.2959
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发表时间：
2019
影响因子：
3.4
通讯作者：
Colin-York H
中科院分区：
文献类型：
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作者：
Colin-York H
Oxford，United Kingdom，2UCL，伦敦，英国。细胞骨架肌动蛋白动力学对于T细胞活化是必不可少的，T细胞活化是适应性免疫应答中的关键步骤。在活化期间在T细胞和抗原呈递细胞之间形成的紧密的细胞-细胞接触（称为免疫突触）已被证明是一种动态的物理结构，其中产生复杂的机械力。使用一系列的生物物理技术，我们显示的证据表明，从事T细胞受体的抗原的结合动力学控制的纳米级肌动蛋白组织和力学的免疫突触。通过用一系列抗原刺激表达特异性T细胞受体的T细胞，力测量显示T细胞受体在活化期间经历的峰值力与刺激抗原的动力学无关。相反，在突触的肌动蛋白逆行流速的定量揭示了一个惊人的依赖于抗原动力学。总之，这些发现表明，肌动蛋白细胞骨架的动态积极调整，以正常化的T细胞受体所经历的抗原特异性的方式。因此，调节肌动蛋白动态响应抗原动力学可能是一种机制，允许T细胞通过调节T细胞受体信号传导的长度和时间尺度来调节其活化反应。
Oxford, United Kingdom, 2UCL, London, United Kingdom. Cytoskeletal actin dynamics are essential for T-cell activation, a key step in the adaptive immune response. The intimate cell-cell contact that forms between the T-cell and antigen presenting cell during activation, known as the immunological synapse, has been shown to be a dynamic, physical structure where complex mechanical forces are generated. Using a range of biophysical techniques, we show evidence that the binding kinetics of the antigen engaging the T-cell receptor controls the nanoscale actin organization and mechanics of the immune synapse. By stimulating T-cells expressing a specific T-cell receptor by a range of antigens, force measurements revealed that the peak force experienced by the T-cell receptor during activation was independent of the kinetics of the stimulating antigen. Conversely, quantification of the actin retrograde flow velocity at the synapse revealed a striking dependence on the antigen kinetics. Taken together, these findings suggest that the dynamics of the actin cytoskeleton actively adjusted to normalize the force experienced by the T-cell receptor in an antigen specific manner. Consequently, tuning actin dynamics in response to antigen kinetics may thus be a mechanism that allows T cells to tune their activation response by adjusting the length-and time-scale of T-cell receptor signaling.