Cullinan Patrick, Sperling Anne I, Burkhardt Janis K
Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA.
Immunol Rev. 2002 Nov;189:111-22. doi: 10.1034/j.1600-065x.2002.18910.x.
While much interest has focused on the finding that T cell-antigen presenting cell (APC) interaction induces the recruitment of proteins to the immunological synapse (IS), we have recently discovered that APC binding induces the formation of a novel protein complex distal to the site of T-cell receptor ligation. This 'distal pole complex' (DPC) is important for appropriate T-cell activation, functioning either to remove proteins from the synapse or as a signaling complex in its own right. The first component of the DPC to be identified was CD43, a cell-surface mucin that has been proposed to function as a negative regulator of T-cell signaling. CD43 movement was found to depend on ezrin and moesin, members of the ERM family, which serve to link CD43 and other cargo molecules to the actin cytoskeleton. ERM proteins interact with several other important surface receptors and cytoplasmic signaling molecules, some of which we have identified as additional components of the DPC. Disruption of the DPC leaves early T-cell activation events intact but affects cytokine expression. Here, we review what is currently known about the formation and function of the DPC and speculate on how this novel protein complex serves to facilitate T-cell activation.
虽然很多研究兴趣都集中在T细胞与抗原呈递细胞（APC）相互作用会诱导蛋白质募集到免疫突触（IS）这一发现上，但我们最近发现，APC结合会诱导在T细胞受体连接位点远端形成一种新型蛋白质复合物。这种“远端极复合物”（DPC）对于适当的T细胞激活很重要，其作用要么是从突触中移除蛋白质，要么本身作为一种信号复合物。DPC中第一个被鉴定出来的成分是CD43，一种细胞表面粘蛋白，有人提出它作为T细胞信号传导的负调节因子发挥作用。发现CD43的移动依赖于ERM家族成员埃兹蛋白和膜突蛋白，它们将CD43和其他货物分子连接到肌动蛋白细胞骨架上。ERM蛋白与其他几个重要的表面受体和细胞质信号分子相互作用，我们已将其中一些鉴定为DPC的其他成分。DPC的破坏使早期T细胞激活事件保持完整，但会影响细胞因子表达。在这里，我们综述了目前关于DPC形成和功能的已知信息，并推测这种新型蛋白质复合物如何促进T细胞激活。
