Essential role for cathepsin S in MHC class II - Associated invariant chain processing and peptide loading
Essential role for cathepsin S in MHC class II - Associated invariant chain processing and peptide loading
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DOI：
10.1016/s1074-7613(00)80249-6
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发表时间：
1996-04-01
期刊：
影响因子：
32.4
通讯作者：
Chapman, HA
中科院分区：
文献类型：
--
作者：
Riese, RJ;Wolf, PR;Chapman, HA
通过蛋白水解破坏ii是MHC II类分子结合抗原肽以及将所得复合物转运至细胞表面所必需的。半胱氨酸蛋白酶组织蛋白酶S在脾、淋巴细胞、单核细胞和其他II类阳性细胞中高度表达，并且可以用干扰素-γ诱导。特异性抑制B类淋巴母细胞中的组织蛋白酶S阻止了II的完全蛋白水解，导致II类相关的13 kDa II片段在体内积累。因此，SDS稳定复合物的形成显著减少。纯化的组织蛋白酶S，而不是组织蛋白酶B、H或D，从α β li三聚体特异性消化Ii，产生能够在体外结合外源添加的肽的α β-CLIP复合物。因此，组织蛋白酶S在B细胞中对于使II类分子有能力结合肽所必需的有效II蛋白水解是必需的。
Destruction of ii by proteolysis is required for MHC class II molecules to bind antigenic peptides, and for transport of the resulting complexes to the cell surface. The cysteine protease cathepsin S is highly expressed in spleen, lymphocytes, monocytes, and other class Ii-positive cells, and is inducible with interferon-gamma. Specific inhibition of cathepsin S in B lymphoblastoid cells prevented complete proteolysis of ii, resulting in accumulation of a class II-associated 13 kDa ii fragment in vivo. Consequently, the formation of SDS-stable complexes was markedly reduced. Purified cathepsin S, but not cathepsin B, H, or D, specifically digested Ii from alpha beta li trimers, generating alpha beta-CLIP complexes capable of binding exogenously added peptide in vitro. Thus, cathepsin S is essential in B cells for effective ii proteolysis necessary to render class II molecules competent for binding peptides.