Micro-adhesion rings surrounding TCR microclusters are essential for T cell activation.
Micro-adhesion rings surrounding TCR microclusters are essential for T cell activation.
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DOI：
10.1084/jem.20151088
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发表时间：
2016-07-25
期刊：
影响因子：
--
通讯作者：
Saito T
中科院分区：
文献类型：
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作者：
Hashimoto-Tane A;Sakuma M;Ike H;Yokosuka T;Kimura Y;Ohara O;Saito T
Saito等人描述了一个围绕T细胞受体微簇的黏附分子环，对早期T细胞激活至关重要。免疫突触（IS）在T细胞和抗原呈递细胞之间的界面形成，是获得性免疫启动的标志。T细胞激活始于T细胞受体（TCR）微簇（MCs），其中TCR和信号分子在is形成之前聚集在界面上。我们发现，在激活的早期阶段，每个TCR-MC都有一个由整合素和黏附分子组成的环状结构，其结构与微尺度上的is相似。微粘附环由LFA-1、黏附分子paxillin和Pyk2以及myosin II （MyoII）组成，并通过LFA-1的外向内信号得到F-actin核和MyoII活性的支持。微粘附环的形成是短暂的，但在弱TCR刺激下招募T细胞（LAT）和SLP76激活的连接体时，微粘附环的形成尤其持续。微粘附环的扰动导致TCR-MC发育受损，导致细胞信号和细胞功能受损。因此，由核心TCR-MC和周围微粘附环组成的突触样结构是通过整合素内外信号初始激活T细胞的关键结构。
Saito et al. describe a ring of focal adhesion molecules that surrounds T cell receptor microclusters and is essential for early T cell activation. The immunological synapse (IS) formed at the interface between T cells and antigen-presenting cells represents a hallmark of initiation of acquired immunity. T cell activation is initiated at T cell receptor (TCR) microclusters (MCs), in which TCRs and signaling molecules assemble at the interface before IS formation. We found that each TCR-MC was transiently bordered by a ring structure made of integrin and focal adhesion molecules in the early phase of activation, which is similar in structure to the IS in microscale. The micro–adhesion ring is composed of LFA-1, focal adhesion molecules paxillin and Pyk2, and myosin II (MyoII) and is supported by F-actin core and MyoII activity through LFA-1 outside-in signals. The formation of the micro–adhesion ring was transient but especially sustained upon weak TCR stimulation to recruit linker for activation of T cells (LAT) and SLP76. Perturbation of the micro–adhesion ring induced impairment of TCR-MC development and resulted in impaired cellular signaling and cell functions. Thus, the synapse-like structure composed of the core TCR-MC and surrounding micro–adhesion ring is a critical structure for initial T cell activation through integrin outside-in signals.