CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase association and activation.
CD28-mediated costimulation in the absence of phosphatidylinositol 3-kinase association and activation.
复制标题
在没有磷脂酰肌醇 3-激酶关联和激活的情况下，CD28 介导的共刺激。
DOI：
10.1128/mcb.15.12.6820
复制
发表时间：
1995
影响因子：
5.3
通讯作者：
Stein,PH
中科院分区：
文献类型：
--
作者：
Crooks,ME;Littman,DR;Carter,RH;Fearon,DT;Weiss,A;Stein,PH
T细胞活化涉及两种不同的信号转导途径。抗原特异性信号传导事件由T细胞受体识别由主要组织相容性复合物分子呈递的同源肽而启动。最佳T细胞活化和克服无反应性诱导所需的共刺激信号可以由同型二聚体T细胞糖蛋白CD 28通过其与抗原呈递细胞上的反受体B7-1和B7-2的相互作用提供。CD 28的连接导致其在酪氨酸上的磷酸化以及随后的磷脂酰肌醇3-激酶（PI 3-激酶）的募集和活化。已经表明，诱导的CD 28和PI 3-激酶的联合是共刺激所必需的。我们在这里报告，连接的CD 19，异源B细胞受体，也与PI 3-激酶连接后激活，未能共刺激白细胞介素-2的生产。此外，PI 3-激酶活性的药理学抑制未能阻断CD 28介导的共刺激。通过突变分析，我们证明了PI 3-激酶与CD 28的结合的破坏也没有消除共刺激。这些结果表明，PI 3-激酶与CD 28的关联既不是必要的，也不足以共刺激白细胞介素2的产生。最后，我们确定了CD 28介导的共刺激活性所需的特定氨基酸残基。
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.