The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1549-54. doi: 10.1073/pnas.1017340108. Epub 2011 Jan 4.
Naïve T lymphocytes display weaker and slower responses than antigen-experienced cells for reasons that are not well understood. Here we show that T-cell receptor (TCR) stimulation induces distinct ERK and p38 phosphorylation patterns in naïve and antigen-experienced human T cells, and that these contribute to the differential responses shown by these cells. Specifically, TCR ligation triggers the activation of the ERK pathway in naïve cells. This phosphorylation of ERK attenuates subsequent calcium influx and accelerates the degradation of the signalsome. In contrast, anti-CD3 stimulation of experienced cells results in the phosphorylation of p38 via an association with Discs large (Dlg). Thus, there are distinct signaling pathways triggered by TCR ligation that impair signaling in naïve cells and facilitate it in antigen-experienced cells.
幼稚 T 淋巴细胞的反应比抗原经验细胞弱且慢，但原因尚不清楚。在这里，我们表明 T 细胞受体 (TCR) 刺激在幼稚和抗原经验的人类 T 细胞中诱导不同的 ERK 和 p38 磷酸化模式，并且这些模式有助于这些细胞表现出的不同反应。具体而言，TCR 交联在幼稚细胞中触发 ERK 途径的激活。ERK 的这种磷酸化减弱了随后的钙内流并加速了信号转导体的降解。相比之下，抗 CD3 刺激经验细胞导致通过与 Discs large (Dlg) 相关的 p38 磷酸化。因此，由 TCR 交联触发的不同信号通路会削弱幼稚细胞中的信号传导，并促进抗原经验细胞中的信号传导。
