...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand.
【24h】

Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand.

机译：I型人T细胞淋巴病毒I型税收特异性CD8 T细胞通过改变的肽配体的差异激活增殖和细胞毒性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Human T-cell leukemia virus type I (HTLV-I) gives rise to a neurologic disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the pathogenesis of the disease is unknown, the presence of a remarkably high frequency of Tax-specific, cytotoxic CD8 T cells may suggest a role of these cells in the development of HAM/TSP. Antigen-mediated signaling in a CD8 T-cell clone specific for the Tax(11-19) peptide of HTLV-I was studied using analog peptides substituted in their T-cell receptor contact residues defined by x-ray crystallographic data of the Tax(11-19) peptide in the groove of HLA-A2. CD8 T-cell stimulation with the wild-type peptide antigen led to activation of p56lck kinase activity, interleukin 2 secretion, cytotoxicity, and clonal expansion. A Tax analog peptide with an alanine substitution of the T-cell receptor contact residue tyrosine-15 induced T-cell-mediated cytolysis without activation of interleukin 2 secretion or proliferation. Induction of p56lck kinase activity correlated with T-cell-mediated cytotoxicity, whereas interleukin 2 secretion correlated with [3H]thymidine incorporation and proliferation. Moreover, Tax peptide analogs that activated the tyrosine kinase activity of p56lck could induce unresponsiveness to secondary stimulation with the wild-type peptide. These observations show that a single amino acid substitution in a T-cell receptor contact residue of Tax can differentially signal CD8 T cells and further demonstrate that primary activation has functional consequences for the secondary response of at least some Tax-specific CD8 T cells to HTLV-I-infected target cells.
机译：I型人T细胞白血病病毒（HTLV-1）引起了一种神经系统疾病，称为HTLV-1相关性脊髓病/热带痉挛性轻瘫（HAM / TSP）。尽管该疾病的发病机理尚不清楚，但存在高频率的Tax特异性细胞毒性CD8 T细胞的存在可能暗示了这些细胞在HAM / TSP发育中的作用。使用替代X射线晶体学数据定义的T细胞受体接触残基中的类似肽研究了对HTLV-1的Tax（11-19）肽具有特异性的CD8 T细胞克隆中的抗原介导信号转导。 11-19）肽在HLA-A2的凹槽中。用野生型肽抗原刺激CD8 T细胞可激活p56lck激酶活性，白介素2分泌，细胞毒性和克隆扩增。用T细胞受体接触残基酪氨酸15的丙氨酸取代的Tax类似肽，在不激活白介素2分泌或增殖的情况下诱导T细胞介导的细胞溶解。 p56lck激酶活性的诱导与T细胞介导的细胞毒性有关，而白介素2的分泌与[3H]胸苷的掺入和增殖有关。此外，激活p56lck酪氨酸激酶活性的Tax肽类似物可能诱导对野生型肽的二次刺激无反应。这些观察结果表明，Tax的T细胞受体接触残基中的单个氨基酸取代可以差异地传递CD8 T细胞信号，并进一步证明初级激活对至少一些Tax特异性CD8 T细胞对HTLV的次级反应具有功能性影响-I感染的靶细胞。

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