Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1.

Differential requirement for cathepsin D for processing of the full length and C-terminal fragment of the malaria antigen MSP1.
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疟疾抗原MSP1的全长和C末端片段处理组织蛋白酶D的差分需求。

DOI:
10.1371/journal.pone.0024886
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Chain BM
Chain BM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tulone C;Sponaas AM;Raiber EA;Tabor AB;Langhorne J;Chain BM

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裂殖子表面蛋白1在疟原虫裂殖子表面表达,对疟原虫侵入红细胞非常重要。MSP 1特异性CD 4 T细胞反应和抗体可以在疟疾实验模型中赋予保护性免疫。在这项研究中,我们探讨的贡献,组织蛋白酶D和E,两个天冬氨酸蛋白酶先前参与抗原加工,产生MSP 1的CD 4 T细胞表位的介绍。组织蛋白酶D(一种晚期内体/溶酶体酶)的缺乏与骨髓来源的树突状细胞体外处理来自受感染红细胞的表位MSP 1后和脾CD 11 c+树突状细胞体内处理后MSP 1的呈递减少相关。相比之下,MSP 1的可溶性重组蛋白片段的加工和呈递不受组织蛋白酶D的缺乏的影响,但是当组织蛋白酶D和E两者都不存在时被抑制。因此,不同蛋白酶在产生CD 4 T细胞库中的作用取决于抗原被引入免疫系统的背景。
Merozoite Surface Protein 1 is expressed on the surface of malaria merozoites and is important for invasion of the malaria parasite into erythrocytes. MSP1-specific CD4 T cell responses and antibody can confer protective immunity in experimental models of malaria. In this study we explore the contributions of cathepsins D and E, two aspartic proteinases previously implicated in antigen processing, to generating MSP1 CD4 T-cell epitopes for presentation. The absence of cathepsin D, a late endosome/lysosomal enzyme, is associated with a reduced presentation of MSP1 both following in vitro processing of the epitope MSP1 from infected erythrocytes by bone marrow-derived dendritic cells, and following in vivo processing by splenic CD11c+ dendritic cells. By contrast, processing and presentation of the soluble recombinant protein fragment of MSP1 is unaffected by the absence of cathepsin D, but is inhibited when both cathepsin D and E are absent. The role of different proteinases in generating the CD4 T cell repertoire, therefore, depends on the context in which an antigen is introduced to the immune system.
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