Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8+ T Cell Responses
Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8+ T Cell Responses
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DOI：
10.1016/j.celrep.2016.04.002
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发表时间：
2016-05-03
期刊：
影响因子：
8.8
通讯作者：
Gannage, Monique
中科院分区：
文献类型：
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作者：
Loi, Monica;Mueller, Anne;Gannage, Monique
巨自噬机制与 MHC II 类限制性抗原呈递有关。在这里，我们报告这种机制有助于 MHC I 类分子的内化。在缺乏自噬因子 Atg5 和 Atg7 的情况下，由于内吞作用和降解减少，MHC I 类表面水平升高。如果 AAK1 无法通过 Atg8/LC3B 招募，则 MHC I 类分子的内化效率会降低。在缺乏 Atg 依赖性 MHC I 类内化的情况下，树突状细胞在体外和体内更有效地刺激 CD8(+) T 细胞反应。在病毒感染期间，Atg5 的缺乏会导致体内流感和 LCMV 特异性 CD8(+) T 细胞反应增强。流感特异性 CD8(+) T 细胞反应升高与更好地免疫控制这种感染有关。因此，巨自噬机制通过支持 MHC II 类但损害 MHC I 类限制性抗原呈递来协调 T 细胞免疫。
The macroautophagy machinery has been implicated in MHC class II restricted antigen presentation. Here, we report that this machinery assists in the internalization of MHC class I molecules. In the absence of the autophagy factors Atg5 and Atg7, MHC class I surface levels are elevated due to decreased endocytosis and degradation. Internalization of MHC class I molecules occurs less efficiently if AAK1 cannot be recruited via Atg8/LC3B. In the absence of Atg-dependent MHC class I internalization, dendritic cells stimulate CD8(+) T cell responses more efficiently in vitro and in vivo. During viral infections, lack of Atg5 results in enhanced influenzaand LCMV-specific CD8(+) T cell responses in vivo. Elevated influenza-specific CD8(+) T cell responses are associated with better immune control of this infection. Thus, the macroautophagy machinery orchestrates T cell immunity by supporting MHC class II but compromises MHC class I restricted antigen presentation.