LFA-1 Regulates CD8+ T Cell Activation via T Cell Receptor-mediated and LFA-1-mediated Erk1/2 Signal Pathways
LFA-1 Regulates CD8+ T Cell Activation via T Cell Receptor-mediated and LFA-1-mediated Erk1/2 Signal Pathways
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DOI：
10.1074/jbc.m109.002865
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发表时间：
2009-07-31
影响因子：
4.8
通讯作者：
Ma, Qing
中科院分区：
文献类型：
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作者：
Li, Dan;Molldrem, Jeffrey J.;Ma, Qing
LFA-1通过免疫突触调节T细胞的活化和信号转导。T细胞受体(TCR)刺激迅速激活LFA-1，LFA-1提供独特的LFA-1依赖信号来促进T细胞活化。然而，调控这些过程的详细分子途径以及LFA-1促进TCR激活的确切机制仍不清楚。我们发现在CD8(+)T细胞中，LFA-1直接参与TCR刺激的ERK1/2信号转导。TCR介导的ERK1/2信号通路需要LFA-1的存在，而不是配体结合。LFA-1缺陷的T细胞在持续的ERK1/2信号和TCR/CD3聚集方面存在缺陷，从而阻止MTOC重定向、细胞周期进展和有丝分裂。LFA-1在免疫突触的背景下调节TCR介导的ERK1/2信号通路，以募集和放大ERK1/2信号。此外，LFA-1与ICAM-1连接产生一个额外的ERK1/2信号，它与现有的TCR介导的ERK1/2信号协同作用，增强T细胞的激活。因此，LFA-1通过两条不同的信号通路参与CD8(+)T细胞的激活。我们证明，LFA-1的功能是通过免疫突触增强TCR信号，并在CD8(+)T细胞激活中传递不同的信号。
LFA-1 regulates T cell activation and signal transduction through the immunological synapse. T cell receptor (TCR) stimulation rapidly activates LFA-1, which provides unique LFA-1-dependent signals to promote T cell activation. However, the detailed molecular pathways that regulate these processes and the precise mechanism by which LFA-1 contributes to TCR activation remain unclear. We found LFA-1 directly participates in Erk1/2 signaling upon TCR stimulation in CD8(+) T cells. The presence of LFA-1, not ligand binding, is required for the TCR-mediated Erk1/2 signal pathway. LFA-1-deficient T cells have defects in sustained Erk1/2 signaling and TCR/CD3 clustering, which subsequently prevents MTOC reorientation, cell cycle progression, and mitosis. LFA-1 regulates the TCR-mediated Erk1/2 signal pathway in the context of immunological synapse for recruitment and amplification of the Erk1/2 signal. In addition, LFA-1 ligation with ICAM-1 generates an additional Erk1/2 signal, which synergizes with the existing TCR-mediated Erk1/2 signal to enhance T cell activation. Thus, LFA-1 contributes to CD8(+) T cell activation through two distinct signal pathways. We demonstrated that the function of LFA-1 is to enhance TCR signaling through the immunological synapse and deliver distinct signals in CD8(+) T cell activation.