In vivo requirement for Atg5 in antigen presentation by dendritic cells.
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.
Lee
Heung Kyu
HK
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Mattei
Lisa M
LM
Steinberg
Benjamin E
BE
Alberts
Philipp
P
Lee
Yun Hee
YH
Chervonsky
Alexander
A
Mizushima
Noboru
N
Grinstein
Sergio
S
Iwasaki
Akiko
A
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000071187:Autophagy-Related Protein 5; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011828:Radiation Chimera
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000949:Histocompatibility Antigens Class II; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering