Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8+ T Cell Responses
Monica Loi,
Anne Müller,
Karin Steinbach,
Jennifer Niven,
Rosa Barreira da Silva,
Petra Paul,
Laure-Anne Ligeon,
Assunta Caruso,
Randy A. Albrecht,
Andrea C. Becker,
Nicolas Annaheim,
Heike Nowag,
Jörn Dengjel,
Adolfo García-Sastre,
Doron Merkler,
Christian Münz,
Monique Gannagé
Affiliations
Monica Loi
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Anne Müller
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Karin Steinbach
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland
Jennifer Niven
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland
Rosa Barreira da Silva
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Petra Paul
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Laure-Anne Ligeon
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Assunta Caruso
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland
Randy A. Albrecht
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Andrea C. Becker
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
Nicolas Annaheim
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Heike Nowag
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Jörn Dengjel
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
Adolfo García-Sastre
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Doron Merkler
Department of Pathology and Immunology, School of Medicine, University of Geneva, 1211 Geneva, Switzerland
Christian Münz
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
Monique Gannagé
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, 8057 Zürich, Switzerland
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.
