T cell receptor microcluster transport through molecular mazes reveals mechanism of translocation
T cell receptor microcluster transport through molecular mazes reveals mechanism of translocation
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DOI：
10.1529/biophysj.107.119099
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发表时间：
2008-04-15
影响因子：
3.4
通讯作者：
Groves, Jay T.
中科院分区：
文献类型：
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作者：
DeMond, Andrew L.;Mossman, Kaspar D.;Groves, Jay T.
T 细胞对肽抗原的识别涉及 T 细胞受体 (TCR) 与其他共刺激和信号分子的协调运动。由此产生的空间组织结构统称为免疫突触。通过使用纳米图案支持的膜将 TCR 引导成替代图案，促进了空间组织在 TCR 信号传导中作用的实验研究。在这里，我们研究了底物结构重定向 TCR 传输的机制。使用流跟踪算法，在各种约束几何形状下的突触形成过程中跟踪每个细胞内 TCR 簇的整体。初始团簇形成后不久，就会形成类似 20 nm/s 的协调向心流。遇到基底施加的约束的簇会偏转，并以与首选向心方向的相对运动角度成比例的速度平行于约束移动。 TCR 运输由肌动蛋白聚合驱动，并且在突触形成过程中的各个时间点对 F-肌动蛋白的分布进行成像。在早期时间点，底物限制对肌动蛋白分布没有显着影响。在后来的时间点，观察到了适度的差异。这些数据与 TCR 与细胞骨架流动耦合的摩擦模型一致，该模型允许滑动。讨论了该模型对细胞表面分子空间排序的影响。
Recognition of peptide antigen by T cells involves coordinated movement of T cell receptors (TCRs) along with other costimulatory and signaling molecules. The spatially organized configurations that result are collectively referred to as the immunological synapse. Experimental investigation of the role of spatial organization in TCR signaling has been facilitated by the use of nanopatterned-supported membranes to direct TCR into alternative patterns. Here we study the mechanism by which substrate structures redirect TCR transport. Using a flow-tracking algorithm, the ensemble of TCR clusters within each cell was tracked during synapse formation under various constraint geometries. Shortly after initial cluster formation, a coordinated centripetal flow of similar to 20 nm/s develops. Clusters that encounter substrate-imposed constraint are deflected and move parallel to the constraint at speeds that scale with the relative angle of motion to the preferred centripetal direction. TCR transport is driven by actin polymerization, and the distribution of F-actin was imaged at various time points during the synapse formation process. At early time points, there is no significant effect on actin distribution produced by substrate constraints. At later time points, modest differences were observed. These data are consistent with a frictional model of TCR coupling to cytoskeletal flow, which allows slip. Implications of this model regarding spatial sorting of cell-surface molecules are discussed.