• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase association and activation.
【24h】

CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase association and activation.

机译：在没有磷脂酰肌醇3-激酶结合和激活的情况下，CD28介导的共刺激。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

T-cell activation involves two distinct signal transduction pathways. Antigen-specific signaling events are initiated by T-cell receptor recognition of cognate peptide presented by major histocompatibility complex molecules. Costimulatory signals, which are required for optimal T-cell activation and for overcoming the induction of anergy, can be provided by the homodimeric T-cell glycoprotein CD28 through its interaction with the counterreceptors B7-1 and B7-2 on antigen-presenting cells. Ligation of CD28 results in its phosphorylation on tyrosines and the subsequent recruitment and activation of phosphatidylinositol 3-kinase (PI 3-kinase). It has been suggested that the induced association of CD28 and PI 3-kinase is required for costimulation. We report here that ligation of CD19, a heterologous B-cell receptor that also associates with and activates PI 3-kinase upon ligation, failed to costimulate interleukin-2 production. Moreover, pharmacological inhibition of PI 3-kinase activity failed to block costimulation mediated by CD28. By mutational analysis, we demonstrate that disruption of PI 3-kinase association with CD28 also did not abrogate costimulation. These results argue that PI 3-kinase association with CD28 is neither necessary nor sufficient for costimulation of interleukin-2 production. Finally, we identify specific amino acid residues required for CD28-mediated costimulatory activity.
机译：T细胞激活涉及两个不同的信号转导途径。抗原特异性信号转导事件是由主要组织相容性复合物分子呈现的同源肽的T细胞受体识别引发的。同二聚体T细胞糖蛋白CD28通过与抗原呈递细胞上的反受体B7-1和B7-2相互作用，可以提供最佳T细胞活化和克服无能诱导所需的共刺激信号。 CD28的连接会导致其在酪氨酸上的磷酸化，并随后募集和激活磷脂酰肌醇3-激酶（PI 3-激酶）。已经提出，共刺激需要CD28和PI 3-激酶的诱导缔合。我们在这里报告说，CD19的连接，一种异源B细胞受体，在连接后也与PI 3激酶相关联并激活，其未能共刺激白介素2的产生。而且，药理学上对PI 3激酶活性的抑制未能阻止由CD28介导的共刺激。通过突变分析，我们证明与CD28的PI 3-激酶关联的破坏也不会废除协同刺激。这些结果表明，PI 3-激酶与CD28的结合对于白介素2产生的共刺激既不是必需的也不是足够的。最后，我们确定CD28介导的共刺激活性所需的特定氨基酸残基。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号