Role of phosphatidylinositol-anchored proteins in T cell activation.
Role of phosphatidylinositol-anchored proteins in T cell activation.
复制标题
磷脂酰肌醇锚定蛋白在 T 细胞激活中的作用。
作者：
D. Presky;M. G. Low;E. Shevach
一类新的细胞表面蛋白通过磷脂酰肌醇（PI）-聚糖锚定结构附着在质膜上，这些蛋白可以通过PI特异性磷脂酶C（PI-PLC）从细胞表面选择性去除。酶处理导致几种PI锚定蛋白的细胞表面表达的延长减少。T细胞的活化导致PI-PLC从活化的T细胞去除PI锚定的表面蛋白的能力显著降低。PI-PLC敏感性的这种降低可能反映了PI-聚糖锚定结构或一般膜性质的改变，这使得PI锚定蛋白质无法接近酶。当小鼠T淋巴细胞用PI-PLC处理，然后用Con A、钙离子载体A23187和PMA或抗CD 3 mAb刺激时，对Con A刺激的反应被抑制90%，而对离子载体和PMA或抗CD 3的反应不受影响。PI锚定蛋白的去除抑制了响应于Con A的激活过程中的早期事件，因为PI PLC处理抑制了IL-2产生和IL-2 R表达。Con A反应的抑制是继发于从应答T细胞群体中去除PI连接蛋白，因为PI-PLC处理T耗竭的脾细胞并不改变其作为辅助细胞来源的能力。去除鼠T细胞上已知的PI连接蛋白Thy-1和Ly-6不太可能完全解释Con A反应的抑制，因为缺乏这些表面蛋白的细胞系M2 B3对Con A刺激反应正常。这些研究表明，一个或多个PI锚定的T细胞蛋白在Con A活化的早期步骤中发挥重要作用，可能涉及T细胞-辅助细胞相互作用。相反，通过TCR/CD 3复合物的直接交联刺激T细胞的能力不依赖于这些PI锚定蛋白的存在。
A novel class of cell surface proteins are attached to the plasma membrane via a phosphatidylinositol (PI)-glycan anchoring structure, and these proteins can be selectively removed from the cell surface by the enzyme PI-specific phospholipase C (PI-PLC). Enzyme treatment led to a prolonged reduction in cell surface expression of several PI-anchored proteins. Activation of T cells led to a marked decrease in the ability of PI-PLC to remove PI-anchored surface proteins from the activated T cells. This decrease in PI-PLC sensitivity may reflect an alteration in the PI-glycan anchoring structures, or in a general membrane property, which renders the PI-anchored proteins inaccessible to the enzyme. When murine T lymphocytes were treated with PI-PLC and then stimulated with either Con A, the calcium ionophore A23187 and PMA, or an anti-CD3 mAb, the response to Con A stimulation was inhibited by 90%, whereas the responses to ionophore and PMA or anti-CD3 were not affected. Removal of PI-anchored proteins inhibited an early event in the activation process in response to Con A because both IL-2 production and IL-2R expression were inhibited by the PI-PLC treatment. Inhibition of the Con A response was secondary to removal of a PI-linked protein from the responder T cell population because PI-PLC treatment of T-depleted spleen cells did not alter their ability to act as a source of accessory cells. It is unlikely that removal of the known PI-linked proteins on murine T cells, Thy-1 and Ly-6, can fully account for the inhibition of Con A response because the cell line M2B3, that lacks these surface proteins, responded normally to Con A stimulation. These studies demonstrate that one or more PI-anchored T cell proteins play an important role in an early step of Con A activation, perhaps involving T cell-accessory cell interactions. In contrast, the ability to stimulate T cells by direct cross-linking of TCR/CD3 complex is not dependent on the presence of these PI-anchored proteins.