不变链蛋白解的发育调节 控制MHCII类 贩卖小鼠树突细胞
1Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA.
Cell
|July 10, 1998
概括
树突细胞 (DCs) 通过调节MHCII类运输来控制抗原呈现. 由囊素C调节的甲素S活性决定了MHCII类是否到达细胞表面或溶解体.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 保护酶的功能 保护酶的功能
背景情况:
- 树突细胞 (DCs) 对于通过抗原呈现启动免疫反应至关重要.
- 在DC上MHCII类分子的表面表达对T细胞激活至关重要.
- 蛋白酶的不变链 (ii) 裂变调节了MHCII类的贩运和呈现.
研究的目的:
- 阐明控制树突细胞 (DCs) 中不变链 (Ii) 裂变的调节机制.
- 为了研究cathepsin S和cystatin C在MHCII类表面表达的发育调节中的作用.
- 了解甲素S和氨酸C之间的平衡如何影响DCs中的抗原呈现能力.
主要方法:
- 在不成熟和成熟的直流中分析不变链 (II) 裂变.
- 评估甲素S活性及其与MHCII类表面表达的相关性.
- 作为甲素S.调节剂的cystatin C表达和局部化的研究.
- 在发育中的DC中,定量化了cystatin C和cathepsin S之间的比率.
主要成果:
- 未成熟的DC表现出较低的cathepsin S活性,导致II链-MHCII类复杂物运输到 lysosomes.
- 成熟的DCs显示了升高的cathepsin S活性,促进MHCII类αβ二聚合物的高效输送到血膜.
- 甲素S活性是通过cystatin C进行翻译后调节的,而不是转录.
- 囊素C与甲素S的比率决定了新合成的MHCII类分子的贩运命运.
结论:
- 在DC中抗原呈现的发育调节由蛋白酶甲素S控制.
- 赛斯塔丁C作为一个关键的内源抑制剂,调节甲素S活性,从而调节MHCII类表面表达.
- 甲素S和氨酸C之间的平衡是DC的功能成熟及其抗原呈现能力的关键决定因素.
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