• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >The role of cysteine proteases in MHC class II antigen processing and presentation.
【24h】

The role of cysteine proteases in MHC class II antigen processing and presentation.

机译：半胱氨酸蛋白酶在MHC II类抗原加工和呈递中的作用。

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

MHC class II molecules present self and foreign antigenic peptides to CD4+ T cells. Specific lysosomal cysteine proteases cathepsin S and cathepsin L are critical for the processing of antigens and are required for the maturation of the MHC class II by degrading the chaperone molecule invariant chain. There is a distinct distribution of these cysteine proteases with cathepsin S expressed in bone marrow derived antigen presenting cells and cathepsin L in thymic epithelium. Macrophages are unique because they contain both active cathepsin S and cathepsin L. Interestingly, macrophages activated to upregulate MHC class II levels on the cell surface with the type-I immune cytokine IFN-gamma, markedly decreases cathepsin L activity to below levels of detection whereas, mature cathepsin L protein levels remain unchanged. Furthermore, our results suggest that there is a potential specific inhibitor of cathepsin L activity. Cathepsin S activity, however, increases in response to treatment with IFN-gamma and in its absence we find an accumulation of invariant chain fragments. Therefore, cathepsin S is responsible for antigen processing and presentation in macrophages. This demonstrates cysteine protease activity is non-redundant and tightly controlled not only by expression but by strategically expressed inhibitors in professional antigen presenting cells.; Non-professional antigen presenting cells have been shown to express low levels of MHC class II or can be induced to transiently express MHC class II on the cell surface. We examined MHC class II levels and invariant chain degradation in mice deficient in either cathepsin S or cathepsin L. Surprisingly, increased MHC class II and accumulated invariant chain fragments were detected in the epithelium of the small and large intestine mice devoid of cathepsin S. We were able to demonstrate for the first time that freshly isolated epithelial cells are capable of internalizing and presenting endogenous antigens and more importantly, that cathepsin S is prominent in this process. Moreover, deficiency in cathepsin L does not affect invariant chain processing or MHC class II levels in epithelial cells lining the intestine. Thus, we have described that all MHC class II antigen presenting cells utilize cathepsin S for invariant chain processing and antigen presentation.
机译：MHC II类分子将自身和外来抗原肽呈递给CD4 + T细胞。特定的溶酶体半胱氨酸蛋白酶组织蛋白酶S和组织蛋白酶L对于抗原的加工至关重要，并且对于MHC II类的成熟是必需的，通过降解伴侣分子不可变链来实现。这些半胱氨酸蛋白酶与组织蛋白酶S在骨髓来源的抗原呈递细胞中表达，而组织蛋白酶L在胸腺上皮中有明显的分布。巨噬细胞是独特的，因为它们同时含有活性组织蛋白酶S和组织蛋白酶L。有趣的是，巨噬细胞被激活以通过I型免疫细胞因子IFN-γ上调细胞表面的MHC II类水平，从而使组织蛋白酶L活性显着降低至检测水平以下，而，成熟的组织蛋白酶L蛋白水平保持不变。此外，我们的结果表明存在潜在的组织蛋白酶L活性特异性抑制剂。但是，组织蛋白酶S活性随着对IFN-γ的处理而增加，并且在不存在的情况下，我们发现恒定链片段的积累。因此，组织蛋白酶S负责巨噬细胞中的抗原加工和呈递。这表明半胱氨酸蛋白酶的活性是非冗余的，不仅通过表达，而且通过在专业抗原呈递细胞中通过策略性表达的抑制剂来严格控制。已显示非专业抗原呈递细胞表达低水平的II类MHC或可诱导其在细胞表面瞬时表达MHC II类。我们在缺乏组织蛋白酶S或组织蛋白酶L的小鼠中检查了II类MHC水平和不变链降解。令人惊讶的是，在缺乏组织蛋白酶S的小肠和大肠小鼠的上皮中检测到II类MHC的增加和累积的不变链片段。首次证明新鲜分离的上皮细胞能够内化并呈递内源性抗原，更重要的是，组织蛋白酶S在此过程中非常重要。此外，组织蛋白酶L的缺乏不会影响肠壁上皮细胞的不变链加工或II类MHC水平。因此，我们已经描述了所有MHC II类抗原呈递细胞利用组织蛋白酶S进行不变链加工和抗原呈递。

著录项

  • 作者

    Beers, Courtney.;

  • 作者单位

    University of Washington.;

  • 授予单位 University of Washington.;
  • 学科 Health Sciences Immunology.; Chemistry Biochemistry.; Biology Cell.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 110 p.
  • 总页数 110
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 预防医学、卫生学;生物化学;细胞生物学;
  • 关键词

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