Lipid rafts mediate association of LFA-1 and CD3 and formation of the immunological synapse of CTL
Lipid rafts mediate association of LFA-1 and CD3 and formation of the immunological synapse of CTL
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DOI：
10.4049/jimmunol.173.5.2960
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Takei, F
中科院分区：
文献类型：
--
作者：
Marwali, MR;MacLeod, MA;Takei, F
脂筏积聚在由TCR/CD 3、LFA-1和信号分子的有组织组装形成的免疫突触中。然而，脂筏在免疫突触形成中的确切作用尚不清楚。在这项研究中，我们表明，LFA-1对CTL是组成型活性和介导的Ag非依赖性结合的CTL表达其配体的靶细胞。CTL上的LFA-1和CD 3，而不是静息T细胞，共定位于脂筏中。CTL上的LFA-1与靶点的结合启动了免疫突触的形成，该免疫突触由分布在细胞接触部位周围的LFA-1、CD 3和神经节苷脂GM 1形成，胆固醇分布更广泛。这种突触的形成是Ag非依赖性的，但是TCR对Ag的识别诱导突触中酪氨酸磷酸化蛋白的积累以及微管组织中心向细胞接触位点的重新分布。我们的研究结果表明，LFA-1招募脂筏和TCR/CD 3到突触，并促进CTL的有效和快速激活。
Lipid rafts accumulate in the immunological synapse formed by an organized assembly of the TCR/CD3, LFA-1, and signaling molecules. However, the precise role of lipid rafts in the formation of the immunological synapse is unclear. In this study, we show that LFA-1 on CTL is constitutively active and mediates Ag-independent binding of CTL to target cells expressing its ligands. LFA-1 and CD3 on CTL, but not resting T cells, colocalize in lipid rafts. Binding of LFA-1 on CTL to targets initiates the formation of the immunological synapse, which is formed by LFA-1, CD3, and ganglioside GM1 distributed in the periphery of the cell contact site and cholesterol is more widely distributed. The formation of this synapse is Ag independent, but the recognition of Ag by the TCR induces accumulation of tyrosine phosphorylated proteins in the synapse as well as redistribution of the microtubule organization center toward the cell contact site. Our results suggest that LFA-1 recruits lipid rafts and the TCR/CD3 to the synapse, and facilitates efficient and rapid activation of CTL.