Hahn W C, Burakoff S J, Bierer B E
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1993 Apr 1;150(7):2607-19.
Through physiologic interactions with its ligands CD58 (lymphocyte function-associated Ag-3, LFA-3) and CD59, the T cell glycoprotein CD2 plays a role in T cell signaling and promotes lymphocyte adhesion. We have recently demonstrated that the interaction of CD2 with CD58 is dynamic: TCR stimulation or treatment with the phorbol ester PMA rapidly up-regulates CD2 ligand avidity, and this regulation requires the carboxyl-terminal asparagine residue of the CD2 cytoplasmic domain. Here we have analyzed the regulation of CD2 avidity for CD58, as assessed by the binding of CD2+ cells to purified CD58 and by the formation of rosettes between CD2+ cells and SRBC. In murine T cell hybridomas transfected with human CD2, we show that, unlike CD2-mediated IL-2 production, cell surface expression of the TCR-CD3 structure is not required for up-regulation of CD2 ligand avidity. TCR-initiated up-regulation of CD2 avidity requires the activity of both protein tyrosine kinases and protein kinase C. Agents which elevate intracellular levels of cAMP also up-regulate CD2 ligand avidity and act either distal to or independently of protein kinase C and protein tyrosine kinases. Cell lines expressing single amino acid substitutions of the carboxyl-terminal asparagine of CD2 are incapable of avidity regulation by TCR signaling, PMA treatment, or elevation of intracellular cAMP levels, demonstrating that each of these stimuli utilizes a common structural element for regulating CD2 avidity. The response to both cAMP and phorbol ester treatment distinguishes the regulation of CD2 avidity from that of a second major adhesion pathway, LFA-1 (CD11a/CD18)/ICAM-1 (CD54) and from that of the TCR coreceptor CD8. These observations identify the signaling events involved in the regulation of CD2 avidity and help to define the signal transduction processes that participate in "inside-out" signaling.
通过与配体CD58（淋巴细胞功能相关抗原-3，LFA-3）和CD59发生生理相互作用，T细胞糖蛋白CD2在T细胞信号传导中发挥作用，并促进淋巴细胞黏附。我们最近证明，CD2与CD58的相互作用是动态的：TCR刺激或用佛波酯PMA处理可迅速上调CD2配体亲和力，且这种调节需要CD2胞质结构域的羧基末端天冬酰胺残基。在此，我们分析了CD2对CD58亲和力的调节，这是通过CD2⁺细胞与纯化的CD58结合以及CD2⁺细胞与SRBC之间形成玫瑰花结来评估的。在转染了人CD2的小鼠T细胞杂交瘤中，我们发现，与CD2介导的IL-2产生不同，TCR-CD3结构的细胞表面表达对于CD2配体亲和力的上调并非必需。TCR引发的CD2亲和力上调需要蛋白酪氨酸激酶和蛋白激酶C的活性。提高细胞内cAMP水平的试剂也会上调CD2配体亲和力，其作用要么在蛋白激酶C和蛋白酪氨酸激酶的下游，要么与之无关。表达CD2羧基末端天冬酰胺单氨基酸取代的细胞系无法通过TCR信号传导、PMA处理或细胞内cAMP水平升高来调节亲和力，这表明这些刺激中的每一种都利用共同的结构元件来调节CD2亲和力。对cAMP和佛波酯处理的反应将CD2亲和力的调节与第二条主要黏附途径LFA-1（CD11a/CD18）/ICAM-1（CD54）以及TCR共受体CD8的调节区分开来。这些观察结果确定了参与CD2亲和力调节的信号事件，并有助于定义参与“由内向外”信号传导的信号转导过程。
