Cytoskeletal polarization of T cells is regulated by an immunoreceptor tyrosine-based activation motif-dependent mechanism.
Cytoskeletal polarization of T cells is regulated by an immunoreceptor tyrosine-based activation motif-dependent mechanism.
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DOI：
10.1083/jcb.140.4.861
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发表时间：
1998-02-23
期刊：
影响因子：
--
通讯作者：
Weiss A
中科院分区：
文献类型：
--
作者：
Lowin-Kropf B;Shapiro VS;Weiss A
抽象的。 T 细胞与适当的抗原呈递细胞 (APC) 的结合会诱导 T 细胞的细胞骨架和分泌装置向 T 细胞抗原受体 (TCR) 和肽/主要组织相容性复合物依赖性过程中的细胞-细胞接触位点快速重新定向。这种 T 细胞极化引导细胞因子和细胞毒性介质向 APC 输送，并有助于效应 T 细胞的高度选择性和特异性作用。为了研究调节 T 淋巴细胞细胞骨架重排的信号通路，我们使用 Jurkat T 细胞作为效应器，并使用涂有各种抗体的细胞大小的乳胶珠作为人工 APC，建立了缀合物形成测定。在这里，我们报告说，根据微管组织中心（MTOC）的重新定向和局部肌动蛋白聚合来判断，涂有 TCR-CD3 复合物特异性抗体的珠子足以诱导 T 细胞向珠子附着位点极化。因此，这些细胞骨架的变化并不依赖于额外的辅助受体的激活。此外，TCR 复合物的单个亚基，即 TCR-ze 和 CD3ε，在诱导细胞骨架极化方面同样有效。然而，基于免疫受体酪氨酸的激活基序 (ITAM) 的诱变（在 TCR-ze 中出现 3 次，在 CD3ε 中出现 1 次）表明，细胞骨架重排的诱导需要至少存在一个完整的 ITAM。与这一结果一致，缺乏功能性 Lck（负责 ITAM 磷酸化的蛋白酪氨酸激酶）会消除 MTOC 重新定向和极化肌动蛋白聚合。抑制剂和瞬时过表达研究均表明 MTOC 重新定向可能在 Ras 激活缺失的情况下发生。我们的结果表明，APC 诱导的 T 细胞极化是 TCR 介导的事件，通过与 TCR 诱导的基因激活相同的信号基序与 TCR 偶联，但其远端信号传导要求不同。
Abstract. Binding of a T cell to an appropriate antigen-presenting cell (APC) induces the rapid reorientation of the T cell cytoskeleton and secretory apparatus towards the cell–cell contact site in a T cell antigen receptor (TCR) and peptide/major histocompatibility complex–dependent process. Such T cell polarization directs the delivery of cytokines and cytotoxic mediators towards the APC and contributes to the highly selective and specific action of effector T cells. To study the signaling pathways that regulate cytoskeletal rearrangements in T lymphocytes, we set up a conjugate formation assay using Jurkat T cells as effectors and cell-sized latex beads coated with various antibodies as artificial APCs. Here, we report that beads coated with antibodies specific for the TCR-CD3 complex were sufficient to induce T cell polarization towards the bead attachment site, as judged by reorientation of the microtubule-organizing center (MTOC) and localized actin polymerization. Thus, these cytoskeletal changes did not depend on activation of additional coreceptors. Moreover, single subunits of the TCR complex, namely TCR-ζ and CD3ε, were equally effective in inducing cytoskeletal polarization. However, mutagenesis of the immunoreceptor tyrosine-based activation motifs (ITAMs), present three times in TCR-ζ and once in CD3ε, revealed that the induction of cytoskeletal rearrangements required the presence of at least one intact ITAM. In agreement with this result, lack of functional Lck, the protein tyrosine kinase responsible for ITAM phosphorylation, abolished both MTOC reorientation and polarized actin polymerization. Both inhibitor and transient overexpression studies demonstrated that MTOC reorientation could occur in the absence of Ras activation. Our results suggest that APC-induced T cell polarization is a TCR-mediated event that is coupled to the TCR by the same signaling motif as TCR-induced gene activation, but diverges in its distal signaling requirements.
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DOI：
10.1084/jem.165.6.1565
发表时间：
1987-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kupfer A;Swain SL;Singer SJ
通讯作者：
Singer SJ
DOI：
10.1073/pnas.92.17.7686
发表时间：
1995-08-15
影响因子：
11.1
作者：
DUDLEY, DT;PANG, L;SALTIEL, AR
通讯作者：
SALTIEL, AR
DOI：
10.1073/pnas.85.22.8613
发表时间：
1988-11-01
影响因子：
11.1
作者：
GOLDSMITH, MA;DAZIN, PF;WEISS, A
通讯作者：
WEISS, A
影响因子：
64.5
作者：
IRVING, BA;WEISS, A
通讯作者：
WEISS, A
DOI：
10.1073/pnas.88.20.8905
发表时间：
1991-10-01
影响因子：
11.1
作者：
LETOURNEUR, F;KLAUSNER, RD
通讯作者：
KLAUSNER, RD