• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Anthrax Toxin as a Molecular Tool for Stimulation of Cytotoxic T Lymphocytes: Disulfide-Linked Epitopes, Multiple Injections, and Role of CD4+ Cells
【24h】

Anthrax Toxin as a Molecular Tool for Stimulation of Cytotoxic T Lymphocytes: Disulfide-Linked Epitopes, Multiple Injections, and Role of CD4+ Cells

机译：炭疽毒素作为刺激细胞毒性T淋巴细胞的分子工具：二硫键连接的抗原决定簇，多次注射和CD4 +细胞的作用

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

摘要

We have previously demonstrated that anthrax toxin-derived proteins, protective antigen (PA) and the amino-terminal portion of lethal factor (LFn), can be used in combination to deliver heterologous molecules to the cytosol of mammalian cells. In this study we examined the ability of an LFn-peptide disulfide-linked heterodimer to prime cytotoxic T lymphocytes (CTL) in the presence of PA. A mutant of LFn that contains a carboxy-terminal reactive cysteine was generated. This form of LFn could be oxidized with a synthetic cysteine containing peptide to form a heterodimer of the protein and peptide. Mice injected with the heterodimer plus PA mounted a peptide-specific CTL response, indicating that this molecule functioned similarly to the genetically fused forms used previously. We also report the results of an analysis of two aspects of this system important for the development of experimental vaccines. First, CD4 knockout mice were unable to generate a CTL response when treated with PA plus an LFn-epitope fusion protein, suggesting that CD4+ helper responses are essential for stimulating specific CTL with the PA-LFn system. Second, we now show that primary injection with this system does not generate any detectable antibody response to the vaccine components and that prior immunization has no effect on priming a CTL response to an unrelated epitope upon subsequent injection.
机译：先前我们已经证明，炭疽毒素衍生的蛋白质，保护性抗原（PA）和致死因子（LFn）的氨基末端部分可以组合使用，以将异源分子传递到哺乳动物细胞的细胞质中。在这项研究中，我们检查了在PA存在下LFn肽二硫键连接的异二聚体对初免细胞毒性T淋巴细胞（CTL）的能力。产生了LFn的突变体，其包含羧基末端反应性半胱氨酸。 LFn的这种形式可以用含有半胱氨酸的合成肽氧化，形成蛋白质和肽的异二聚体。注射了异二聚体和PA的小鼠发生了肽特异性CTL反应，表明该分子的功能与之前使用的遗传融合形式相似。我们还报告了对该系统的两个方面的分析结果，这些方面对开发实验疫苗很重要。首先，用PA加LFn-表位融合蛋白处理后，CD4敲除小鼠不能产生CTL反应，这表明CD4 + 辅助反应对于用PA-LFn系统刺激特异性CTL是必不可少的。其次，我们现在表明，用该系统进行的初次注射不会对疫苗成分产生任何可检测到的抗体反应，并且在随后的注射后，先前的免疫接种对引发针对无关表位的CTL反应没有影响。

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