Cathepsin B cleavage and release of invariant chain from MHC class II molecules follow a staged pattern.
Cathepsin B cleavage and release of invariant chain from MHC class II molecules follow a staged pattern.
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组织蛋白酶 B 的裂解和 MHC II 类分子中不变链的释放遵循分阶段的模式。
DOI：
10.1016/0161-5890(94)90146-5
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发表时间：
1994
影响因子：
3.6
通讯作者：
Humphreys,RE
中科院分区：
文献类型：
--
作者：
Xu,M;Capraro,GA;Daibata,M;Reyes,VE;Humphreys,RE
定义了组织蛋白酶B切割MHC II类α，β -结合不变（Ii）链和释放片段的阶段性模式。在组织蛋白酶B推定的切割位点R78 K80 K83 K86、K137 K143和R151 K154的三个簇中产生Ii链中的电荷丢失突变。共转染入COS 1细胞的HLA-DR 1 α、β和野生型或突变型I基因的产物被组织蛋白酶B切割，并被针对MHC II类链或针对不同I表位的抗体免疫沉淀。在WT II中，组织蛋白酶B消化产生两种形式的p21 I片段：由抗C末端抗体识别的p21和由N末端附近的决定簇的抗体识别的p21。C-末端p21在其形成时从MHC II类α，β链释放，而N-末端p21保持与MHC II类α，β链结合。K137和K143的突变抑制了组织蛋白酶B对N端p21的产生。在R78 K80 K83 K86处的突变导致MHC II类结合的N-末端p21的积累，而在组织蛋白酶B消化后不出现MHC II类结合的p14、p10和p6片段。这些结果表明，组织蛋白酶B切割野生型Ii，首先切割K137-K143，产生MHC II类相关的N-末端p21，然后切割R78-K80-K83-K86，产生p14、p10，最后产生仍与MHC II类α、β链相关的p6。这种分阶段切割和释放的模式可能与调节抗原肽与MHC II类分子结合的协调机制有关。
A staged pattern of cathepsin B cleavage of MHC class II α,β -bound invariant (Ii) chain and release of fragments was defined. Charge-loss mutations in the Ii, chain were created in three clusters of cathepsin B putative cleavage sites R78K80K83K86, K137K143, and R151K154. Products of HLA-DR1 α,β and wild type (WT) or mutant Iigenes, co-transfected into COS1 cells, were cleaved by cathepsin B and immunoprecipitated by antibodies either to MHC class II chains or to different Iiepitopes. In WT Ii, cathepsin B digestion generated two forms of p21 Iifragments: a p21 recognized by anti-C-terminus antibodies and a p21 recognized by an antibody to a determinant near the N-terminus. C-terminal p21 was released from MHC class II α,β chains upon its formation while N-terminal p21 remained associated with MHC class II α,β chains. Mutations at K137K143inhibited the generation of N-terminal p21 by cathepsin B. Mutation at R78K80K83K86led to an accumulation of MHC class II-bound N-terminal p21 without the appearance of MHC class II-bound p14, p10, and p6 fragments after cathepsin B digestion. These results indicate that cathepsin B cleaves wild type Ii, first about K137K143to produce a MHC class II-associated N-terminal p21, which is then cleaved about R78K80K83K86to generate p14, p10 and finally p6 which still associates with MHC class II α,β chains. This pattern of staged cleavage and release of Iimight be related to a concerted mechanism regulating the binding of antigenic peptides to MHC class II molecules.