期刊
IMMUNOLOGY
卷 131, 期 2, 页码 257-267出版社
WILEY
DOI: 10.1111/j.1365-2567.2010.03299.x
关键词
cathepsin L; cytotoxic T cells; cytotoxicity; natural killer cells; perforin deficiency
类别
资金
- Research Agency of the Republic of Slovenia [P-0140]
- Slovenian human resources development and scholarship foundation, Slovenia
- National Health and Medical Research Council (NHMRC) of Australia [454569]
- NMHRC [288999]
- Deutsche Forschungsgemeinschaft [Ho 4007/1-1]
P>The pore-forming protein perforin is synthesized as an inactive precursor in natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), and becomes active when a short C-terminal peptide is cleaved within acidic lysosome-like cytotoxic granules. Although it was shown more than a decade ago that this cleavage is pH dependent and can be inhibited by the generic cysteine cathepsin inhibitor E-64d, no protease capable of processing the perforin C terminus has been identified. Neither is it known whether a single protease is responsible or the processing has inbuilt redundancy. Here, we show that incubation of human NK cells and primary antigen-restricted mouse CTLs with the cathepsin L (CatL) inhibitor L1 resulted in a marked inhibition of perforin-dependent target cell death and reduced perforin processing. In vitro, CatL preferentially cleaved a site on full-length recombinant perforin close to its C terminus. The NK cells of mice deficient in CatL showed a reduction but not a complete absence of processed perforin, indicating that cysteine proteases other than CatL are also able to process perforin. We conclude that granule-bound cathepsins are essential for processing perforin to its active form, and that CatL is an important, but not exclusive, participant in this process.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据