title: In vivo requirement for Atg5 in antigen presentation by dendritic cells.
abstract: 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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Heung Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mattei
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Steinberg
authors.forename: Philipp
authors.initials: P
authors.lastname: Alberts
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Alexander
authors.initials: A
authors.lastname: Chervonsky
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: 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
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000949:Histocompatibility Antigens Class II; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering