Functional Macroautophagy Induction by Influenza A Virus without a Contribution to Major Histocompatibility Complex Class II-Restricted Presentation
Functional Macroautophagy Induction by Influenza A Virus without a Contribution to Major Histocompatibility Complex Class II-Restricted Presentation
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DOI：
10.1128/jvi.02122-10
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发表时间：
2011-07-01
影响因子：
5.4
通讯作者：
Eisenlohr, Laurence C.
中科院分区：
文献类型：
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作者：
Comber, Joseph D.;Robinson, Tara M.;Eisenlohr, Laurence C.
主要组织相容性复合物 (MHC) II 类呈递的肽可源自外源（细胞外）和内源（生物合成）抗原来源。尽管已经报道了几种内源性抗原加工途径，但人们对它们对针对复杂抗原的整体CD4(+)T细胞反应的相对贡献知之甚少。为此，我们使用流感病毒评估了巨自噬的作用，巨自噬是胞浆蛋白通过从头形成囊泡和膜融合而被递送至溶酶体的过程。流感感染引发了高效的巨自噬，并且通过自然运输至自噬体的模型抗原很容易观察到自噬依赖性呈递。此外，增强或抑制巨自噬的治疗可调节这些模型抗原的呈递水平。然而，使用多种抗原呈递细胞（包括原代树突细胞）对受感染小鼠的流感特异性 CD4+ T 细胞进行经过验证的酶联免疫斑点 (ELISpot) 检测，结果显示没有可检测到的巨自噬依赖性成分。相比之下，蛋白酶体依赖性内源性抗原加工对整体流感 CD4(+) 反应的贡献很容易被认识到。巨自噬对 MHC II 类限制性反应的贡献可能因病原体而异。
Major histocompatibility complex (MHC) class II-presented peptides can be derived from both exogenous (extracellular) and endogenous (biosynthesized) sources of antigen. Although several endogenous antigen-processing pathways have been reported, little is known about their relative contributions to global CD4(+) T cell responses against complex antigens. Using influenza virus for this purpose, we assessed the role of macroautophagy, a process in which cytosolic proteins are delivered to the lysosome by de novo vesicle formation and membrane fusion. Influenza infection triggered productive macroautophagy, and autophagy-dependent presentation was readily observed with model antigens that naturally traffic to the autophagosome. Furthermore, treatments that enhance or inhibit macroautophagy modulated the level of presentation from these model antigens. However, validated enzyme-linked immunospot (ELISpot) assays of influenza-specific CD4(+) T cells from infected mice using a variety of antigen-presenting cells, including primary dendritic cells, revealed no detectable macroautophagy-dependent component. In contrast, the contribution of proteasome-dependent endogenous antigen processing to the global influenza CD4(+) response was readily appreciated. The contribution of macroautophagy to the MHC class II-restricted response may vary depending upon the pathogen.