Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016; Department of Pathology, New York University School of Medicine, New York, NY 10026;
J Immunol. 2014 Jul 1;193(1):56-67. doi: 10.4049/jimmunol.1400315. Epub 2014 May 23.
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 pre-existing 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 linker for activation of T cells and growth factor receptor-bound protein 2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could explain, in part, the rapid kinetics with which TCR signal transduction occurs.
TCR 依赖性信号事件已被观察到发生在 TCR 微簇中。我们发现，一些 TCR 微簇存在于未受刺激的鼠 T 细胞中，这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与低效力配体结合后绝对数量增加。这种增加伴随着细胞铺展的增加，结果是 T 细胞表面 TCR 微簇的密度不是配体效力的强函数。在表征其组成时，我们观察到微簇中 TCR 的数量恒定，磷酸酶 CD45 组成性排除，以及与信号转导适配器 linker for activation of T cells 和 growth factor receptor-bound protein 2 的预关联。在配体结合之前，TCR 微簇处于有利于下游信号转导起始的状态，这可以部分解释 TCR 信号转导发生的快速动力学。
