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免疫蛋白酶体亚基缺陷对两种免疫显性流感病毒特异性CD8 + T细胞反应产生不同影响。

Immunoproteasome subunit deficiencies impact differentially on two immunodominant influenza virus-specific CD8+ T cell responses.

作者信息

Pang Ken C, Sanders Megan T, Monaco John J, Doherty Peter C, Turner Stephen J, Chen Weisan

机构信息

T Cell Laboratory, Melbourne Centre for Clinical Sciences, Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria 3084, Australia.

出版信息

J Immunol. 2006 Dec 1;177(11):7680-8. doi: 10.4049/jimmunol.177.11.7680.

Abstract

Primary CD8+ T cell (T(CD8+)) responses to viruses are directed toward multiple Ags and shaped by both the level of Ag presentation and the underlying Ag-specific T(CD8+) repertoire. The relative importance of these factors in deciding the hierarchy of T(CD8+) responses and how they are influenced by the immunoproteasome are not well understood. Using an influenza infection model in mice deficient in various immunoproteasome subunits, we observe that Ag presentation and T(CD8+) repertoire are altered in an epitope-specific and immunoproteasome subunit-dependent manner. More importantly, we find that the level of Ag presentation and the extent of the underlying repertoire can work either alone or in concert to determine definitively the magnitude of the individual T(CD8+) responses and hence the overall T(CD8+) hierarchy. Together, these results provide a clearer understanding of how immunodominance hierarchies are established.

摘要

原发性CD8⁺T细胞(T(CD8⁺))对病毒的反应针对多种抗原,并由抗原呈递水平和潜在的抗原特异性T(CD8⁺)库塑造。这些因素在决定T(CD8⁺)反应层次结构中的相对重要性以及它们如何受到免疫蛋白酶体的影响尚不清楚。使用缺乏各种免疫蛋白酶体亚基的小鼠流感感染模型,我们观察到抗原呈递和T(CD8⁺)库以表位特异性和免疫蛋白酶体亚基依赖性方式发生改变。更重要的是,我们发现抗原呈递水平和潜在库的程度可以单独或协同作用,以明确确定个体T(CD8⁺)反应的大小,从而确定整体T(CD8⁺)层次结构。这些结果共同为免疫优势层次结构的建立提供了更清晰的理解。

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