A model for the interplay of receptor recycling and receptor-mediated contact in T cells.
A model for the interplay of receptor recycling and receptor-mediated contact in T cells.
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DOI：
10.1371/journal.pone.0000633
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发表时间：
2007-07-25
期刊：
影响因子：
3.7
通讯作者：
Maly IV
中科院分区：
文献类型：
--
作者：
Arkhipov SN;Maly IV
T细胞（TC）内的细胞器向抗原呈递细胞（APC）的定向确保了免疫反应的正确定向，但其定向机制在很大程度上仍然未知。APC的结构动力学与t细胞受体（TCR）的动力学耦合，t细胞受体识别APC表面的抗原。TCR的参与触发其内化，随后通过膜下回收室（RC）延迟极化回收到质膜，该细胞器与TC效应装置共享胞内位置。TCR结合还会触发TC-APC界面扩展，从而使受体进一步结合。为了分析细胞-细胞接触和受体动力学的相互作用，我们建立了一个新的数值模型。新模型显示了实验观察到的在RC附近开始的接触的选择性稳定，并且只有与RC截然相反的接触的瞬态形成。在TC- apc接触在RC的任意方向上启动的一般情况下，建模预测接触动力学和受体回收可以相互作用，导致接触有效地迁移到靠近亚膜RC的TC表面域。使用三维活细胞共聚焦显微镜，我们获得的数据与这种意想不到的行为一致。我们得出结论，TC可以通过将其与TCR的极化胞内交通对齐来稳定其与APC的接触。结果还表明，在不发生胞内易位的情况下，可以实现TC细胞器（如RC和效应器）向APC的定向。
Orientation of organelles inside T cells (TC) toward antigen-presenting cells (APC) ensures that the immune response is properly directed, but the orientation mechanisms remain largely unknown. Structural dynamics of TC are coupled to dynamics of T-cell receptor (TCR), which recognizes antigen on the APC surface. Engagement of the TCR triggers its internalization followed by delayed polarized recycling to the plasma membrane through the submembrane recycling compartment (RC), which organelle shares intracellular location with the TC effector apparatus. TCR engagement also triggers TC-APC interface expansion enabling further receptor engagement. To analyze the interplay of the cell-cell contact and receptor dynamics, we constructed a new numerical model. The new model displays the experimentally observed selective stabilization of the contact initiated next to the RC, and only transient formation of contact diametrically opposed to the RC. In the general case wherein the TC-APC contact is initiated in an arbitrary orientation to the RC, the modeling predicts that the contact dynamics and receptor recycling can interact, resulting effectively in migration of the contact to the TC surface domain adjacent to the submembrane RC. Using three-dimensional live-cell confocal microscopy, we obtain data consistent with this unexpected behavior. We conclude that a TC can stabilize its contact with an APC by aligning it with the polarized intracellular traffic of TCR. The results also suggest that the orientation of TC organelles, such as the RC and the effector apparatus, toward the APC can be achieved without any intracellular translocation of the organelles.
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影响因子：
32.4
作者：
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通讯作者：
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影响因子：
56.9
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作者：
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DOI：
10.1083/jcb.140.4.861
发表时间：
1998-02-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lowin-Kropf B;Shapiro VS;Weiss A
通讯作者：
Weiss A