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Analysis of adhesion molecoles-mediated signal transduction in T cell activation by superantigen.

超抗原激活 T 细胞中粘附分子介导的信号转导分析。

基本信息

批准号：
06807090
负责人：
TANAKA Terukazu
金额：
$ 1.28万
依托单位：
Kagawa Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807090/
关键词：
Superantigen Costimulatory signal CD28 Adhesion molecules Protein kinase C Calphostin C T cell Receptor Vbeta Crosslinking

项目摘要

Recently, we reported that either PMA or CD28 cross-linking synergizes with signals delivered by superantigen and cytokines to induce to proliferation of antigen presenting cells (APC)-depleted T cells. It is suggested that protein kinase C (PKC) activation is involved in the costimulatory signal transduction pathway mediated by CD28 cross-linking. We have examined the effects of CD28 cross-linking on early activation of PKC.First ; a specific inhibitor of PKC,calphostin CInhibition of PKC activity by calphostin C suppressed the response of pure T cells to pep M5, superantigen derived from group A Streptococci strain, in the presence of either autologous APC,PMA,or CD28 cross-linking. It was observed only when calphostin C was added within an first hour after stimulation.Second ; in vitro PKC assayUnder a certain condition of cell activation, PKC is translocated from cytoplasm to plasma membrane where it becomes activated. To determine whether PKC is translocated by stimulation of the signal transduction pathway via CD28, APC-depleted resting T cells were stimulated with either PMA or CD28 cross-linking followed by costimulation with pep M5 plus APC-conditioned medium (SUP) which per se had no effect on PKC activity. PKC activity in both cytosolic and membrane fractions was measured within 45 min after stimulation. Unlike PMA,CD28 cross-linking alone failed to induce an increase in membrane-associated PKC activity. However, in the presence of pep M5 plus SUP,CD28 cross-linking resulted in an increase in membrane-associated PKC activity that reached a three-fold increase in activity by 30 min after addition of stimuli and declined by 45 min. Pep M5 plus SUP alone had no significant effect on membrane PKC activity even when measured at 30 min, the peak of PKC activation.We conclude that CD28 cross-linking augments superantigen-induced signals and activates PKC.

最近，我们报道了PMA或CD 28交联与超抗原和细胞因子传递的信号协同诱导抗原呈递细胞（APC）缺失的T细胞增殖。提示蛋白激酶C（PKC）的激活参与了CD 28交联介导的共刺激信号转导途径。我们已经研究了CD 28交联对PKC早期激活的影响。首先，PKC的特异性抑制剂，calphostin C抑制PKC活性抑制纯T细胞对pep M5的反应，pep M5是来自A组链球菌菌株的超抗原，在自体APC，PMA或CD 28交联的存在下。它被观察到只有当calphostin C在刺激后的第一个小时内加入。第二，体外PKC测定在一定的细胞活化条件下，PKC从细胞质易位到质膜，在那里它变得激活。为了确定PKC是否通过刺激经由CD 28的信号转导途径而移位，用PMA或CD 28交联刺激APC耗尽的静息T细胞，然后用pep M5加APC条件培养基（pepM 5）共刺激，其本身对PKC活性没有影响。PKC活性在胞浆和膜组分刺激后45分钟内测定。与PMA不同，单独的CD 28交联不能诱导膜相关PKC活性的增加。然而，在存在pep M5加β-CD的情况下，CD 28交联导致膜相关PKC活性增加，在加入刺激物后30分钟达到活性的三倍增加，并在45分钟下降。即使在30分钟测量时，单独的Pep M5加β-CD对膜PKC活性也没有显著影响，我们的结论是，CD 28交联增强超抗原诱导的信号并激活PKC。