Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2010 Feb 26;32(2):227-39. doi: 10.1016/j.immuni.2009.12.006. Epub 2010 Feb 18.
Autophagy is known to be important in presentation of cytosolic antigens on MHC class II (MHC II). However, the role of autophagic process in antigen presentation in vivo is unclear. Mice with dendritic cell (DC)-conditional deletion in Atg5, a key autophagy gene, showed impaired CD4(+) T cell priming after herpes simplex virus infection and succumbed to rapid disease. The most pronounced defect of Atg5(-/-) DCs was the processing and presentation of phagocytosed antigens containing Toll-like receptor stimuli for MHC class II. In contrast, cross-presentation of peptides on MHC I was intact in the absence of Atg5. Although induction of metabolic autophagy did not enhance MHC II presentation, autophagic machinery was required for optimal phagosome-to-lysosome fusion and subsequent processing of antigen for MHC II loading. Thus, our study revealed that DCs utilize autophagic machinery to optimally process and present extracellular microbial antigens for MHC II presentation.
自噬被认为在 MHC II（主要组织相容性复合体 II）上呈递细胞质抗原中很重要。然而，自噬过程在体内抗原呈递中的作用尚不清楚。树突状细胞（DC）中关键自噬基因 Atg5 条件性缺失的小鼠在单纯疱疹病毒感染后表现出 CD4(+) T 细胞初始活化受损，并迅速发病死亡。Atg5(-/-) DC 最明显的缺陷是吞噬含有 Toll 样受体刺激物的抗原的加工和呈递，这些抗原可用于 MHC II。相比之下，在没有 Atg5 的情况下，MHC I 上的交叉呈递肽是完整的。尽管代谢自噬的诱导并没有增强 MHC II 的呈递，但自噬机制对于吞噬体到溶酶体融合以及随后用于 MHC II 加载的抗原加工是必需的。因此，我们的研究表明，DC 利用自噬机制来最佳地加工和呈递细胞外微生物抗原，以用于 MHC II 呈递。
