Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+) T Cell Responses.
The macroautophagy machinery has been implicated in MHC class II restricted antigen presentation. Here, we report that this machinery assists in the internalization of MHC class I molecules. In the absence of the autophagy factors Atg5 and Atg7, MHC class I surface levels are elevated due to decreased endocytosis and degradation. Internalization of MHC class I molecules occurs less efficiently if AAK1 cannot be recruited via Atg8/LC3B. In the absence of Atg-dependent MHC class I internalization, dendritic cells stimulate CD8(+) T cell responses more efficiently in vitro and in vivo. During viral infections, lack of Atg5 results in enhanced influenza- and LCMV-specific CD8(+) T cell responses in vivo. Elevated influenza-specific CD8(+) T cell responses are associated with better immune control of this infection. Thus, the macroautophagy machinery orchestrates T cell immunity by supporting MHC class II but compromises MHC class I restricted antigen presentation.
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
Monica
M
Loi
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
Anne
A
Müller
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland.
Karin
K
Steinbach
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland; Division of Rheumatology, Department of Internal Medicine, University Hospital, Geneva 1205, Switzerland.
Jennifer
J
Niven
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
Rosa
R
Barreira da Silva
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
Petra
P
Paul
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
Laure-Anne
LA
Ligeon
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland; Division of Rheumatology, Department of Internal Medicine, University Hospital, Geneva 1205, Switzerland.
Assunta
A
Caruso
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Randy A
RA
Albrecht
Department of Dermatology, Medical Center; ZBSA Center for Biological Systems Analysis; BIOSS Centre for Biological Signalling Studies; and FRIAS Freiburg Institute for Advanced Studies, University of Freiburg, 79104 Freiburg, Germany.
Andrea C
AC
Becker
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
Nicolas
N
Annaheim
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland.
Heike
H
Nowag
Department of Dermatology, Medical Center; ZBSA Center for Biological Systems Analysis; BIOSS Centre for Biological Signalling Studies; and FRIAS Freiburg Institute for Advanced Studies, University of Freiburg, 79104 Freiburg, Germany.
Jörn
J
Dengjel
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Adolfo
A
García-Sastre
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland; Department of Neuropathology, University Medical Center, 37099 Göttingen, Germany.
Doron
D
Merkler
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland. Electronic address: christian.muenz@uzh.ch.
Christian
C
Münz
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland; Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland; Division of Rheumatology, Department of Internal Medicine, University Hospital, Geneva 1205, Switzerland. Electronic address: monique.ghannage@unige.ch.
Monique
M
Gannagé
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics*; D000071193:Autophagy-Related Protein 7 / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
C495773:Atg5 protein, mouse; C502661:Atg7 protein, mouse; D000071187:Autophagy-Related Protein 5; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D000071193:Autophagy-Related Protein 7
AAK1; LCMV; endocytosis; immune control; influenza