Yeh Jung-Hua, Sidhu Sachdev S, Chan Andrew C
Department of Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Cell. 2008 Mar 7;132(5):846-59. doi: 10.1016/j.cell.2008.01.013.
Spatial organization of cellular proteins plays an important role in establishment of cellular polarity to regulate cell division, differentiation, migration, and organogenesis. Activation of T cells by antigen-presenting cells (APCs) results in the formation of an immunological synapse (IS), assembly of a signaling scaffold at the T cell receptor (TCR) contact, cytoskeletal reorganization, and generation of second messengers within the first hours following intercellular contact. We demonstrate here that Crtam (class-I MHC-restricted T-cell associated molecule), an immunoglobulin-superfamily transmembrane protein, coordinates a signaling complex anchored by the Scrib polarity protein to establish a later phase of T cell polarity on a subset of CD4+ T cells >6 hours following activation. Maintenance of this late cellular polarity results in the ability of CD4+Crtam+ T cells to selectively produce more IFNgamma and IL22. Crtam engagement thus modulates signals many hours beyond the initial activation event and dynamically influences the adaptive immune response.
细胞蛋白的空间组织在建立细胞极性以调节细胞分裂、分化、迁移和器官发生过程中起着重要作用。抗原呈递细胞（APC）激活T细胞会导致免疫突触（IS）的形成、在T细胞受体（TCR）接触部位组装信号支架、细胞骨架重组以及细胞间接触后最初几小时内产生第二信使。我们在此证明，Crtam（I类MHC限制性T细胞相关分子），一种免疫球蛋白超家族跨膜蛋白，协调由Scrib极性蛋白锚定的信号复合物，在激活后>6小时在一部分CD4 + T细胞上建立T细胞极性的后期阶段。维持这种晚期细胞极性导致CD4 + Crtam + T细胞能够选择性地产生更多的IFNγ和IL22。因此，Crtam参与在初始激活事件数小时后调节信号，并动态影响适应性免疫反应。
