TCR Microclusters pre-exist and contain molecules necessary for TCR signal transduction.

TCR Microclusters pre-exist and contain molecules necessary for TCR signal transduction.
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DOI:
10.4049/jimmunol.1400315
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发表时间:
2014-07-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Varma R
Varma R
中科院分区:
其他
文献类型:
--
作者:
Crites TJ;Padhan K;Muller J;Krogsgaard M;Gudla PR;Lockett SJ;Varma R

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已经观察到TCR依赖性信号传导事件发生在TCR微簇中。我们发现,一些TCR微簇存在于未受刺激的小鼠T细胞中,表明导致微簇形成的机制不需要配体结合。这些预先存在的微簇在被低效力配体接合后绝对数量增加。这种增加伴随着细胞扩散的增加,结果是T细胞表面上TCR微簇的密度不是配体效力的强函数。在表征其组成时,我们观察到恒定数量的TCR在微簇中,组成性排除磷酸酶CD45,并与信号适配器LAT和Grb2预关联。TCR微簇在配体结合之前以有利于下游信号传导起始的状态存在可以部分解释TCR信号转导发生的快速动力学。
TCR-dependent signaling events have been observed to occur in TCR microclusters. We found that some TCR microclusters are present in unstimulated murine T cells, indicating that the mechanisms leading to microcluster formation do not require ligand binding. These preexisting microclusters increase in absolute number following engagement by low-potency ligands. This increase is accompanied by an increase in cell spreading, with the result that the density of TCR microclusters on the surface of the T cell is not a strong function of ligand potency. In characterizing their composition, we observed a constant number of TCRs in a microcluster, constitutive exclusion of the phosphatase CD45, and preassociation with the signaling adapters LAT and Grb2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could in part explain the rapid kinetics with which TCR signal transduction occurs.
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