Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells
Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells
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DOI：
10.1073/pnas.0710258105
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发表时间：
2007-12-18
影响因子：
11.1
通讯作者：
Vale, Ronald D.
中科院分区：
文献类型：
--
作者：
Kaizuka, Yoshihisa;Douglass, Adam D.;Vale, Ronald D.
T 细胞与抗原呈递细胞 (APC) 相互作用形成“免疫突触”(IS)，这是一种牛眼图案，由富含 T 细胞受体 (TCR) 的中央超分子激活簇组成，周围环绕着一圈粘附分子（外围超分子激活簇）。对于分离 TCR 和粘附分子的机制仍知之甚少。在这里，我们证明永生化的 Jurkat T 细胞与平面脂质双层（模仿 APC）相互作用将形成 IS，从而为研究 IS 形成的细胞生物学过程提供了一个可访问的模型系统。我们发现肌动蛋白依赖性过程导致 TCR 和粘附蛋白在细胞外围聚集，但这些分子似乎在微域形成的最早阶段彼此分离。 TCR 和粘附微结构域附着在肌动蛋白上，并通过逆行流向心携带。然而，只有 TCR 微结构域渗透到肌动蛋白耗尽的细胞中心，而粘附微结构域在没有潜在肌动蛋白细胞骨架的情况下似乎不稳定。我们的结果表明，TCR 和粘附分子在成熟 IS 形成之前就已在空间上相互分离，并且不同的肌动蛋白相互作用有助于形成和维持 IS 最终的牛眼图案。
T cells interacting with antigen-presenting cells (APCs) form an "immunological synapse" (IS), a bull's-eye pattern composed of a central supramolecular activation cluster enriched with T cell receptors (TCRs) surrounded by a ring of adhesion molecules (a peripheral supramolecular activation cluster). The mechanism responsible for segregating TCR and adhesion molecules remains poorly understood. Here, we show that immortalized Jurkat T cells interacting with a planar lipid bilayer (mimicking an APC) will form an IS, thereby providing an accessible model system for studying the cell biological processes underlying IS formation. We found that an actin-dependent process caused TCR and adhesion proteins to cluster at the cell periphery, but these molecules appeared to segregate from one another at the earliest stages of microdomain formation. The TCR and adhesion microdomains attached to actin and were carried centripetally by retrograde flow. However, only the TCR microdomains penetrated into the actin-depleted cell center, whereas the adhesion microdomains appeared to be unstable without an underlying actin cytoskeleton. Our results reveal that TCR and adhesion molecules spatially partition from one another well before the formation of a mature IS and that differential actin interactions help to shape and maintain the final bull's-eye pattern of the IS.