한빛사 논문
Abstract
Heung Kyu Lee,1,7 Lisa M. Mattei,1 Benjamin E. Steinberg,2,3 Philipp Alberts,1,8 Yun Hee Lee,1,9 Alexander Chervonsky,5 Noboru Mizushima,6 Sergio Grinstein,2,4 and Akiko Iwasaki1,*
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
2Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
3Institute of Medical Science
4Department of Biochemistry
University of Toronto, Toronto, Ontario M5S 1A8, Canada
5Department of Pathology, The University of Chicago, Chicago, IL 60637, USA
6Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan
7Present address: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST),Daejeon, 305-701, Republic of Korea
8Present address: Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada
9Present address: Department of Radiation Oncology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
SUMMARY
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, crosspresentation 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.
논문정보
관련 링크
연구자 키워드
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기