1. Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8(+) T Cell Responses.
- Author
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Loi M, Müller A, Steinbach K, Niven J, Barreira da Silva R, Paul P, Ligeon LA, Caruso A, Albrecht RA, Becker AC, Annaheim N, Nowag H, Dengjel J, García-Sastre A, Merkler D, Münz C, and Gannagé M
- Subjects
- Animals, Antigen Presentation immunology, Cells, Cultured, Endocytosis immunology, Histocompatibility Antigens Class II immunology, Humans, Lymphocyte Activation immunology, Macrophages immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Autophagy immunology, Autophagy-Related Protein 5 genetics, Autophagy-Related Protein 7 genetics, CD8-Positive T-Lymphocytes immunology, Dendritic Cells immunology, Histocompatibility Antigens Class I immunology, Influenza A Virus, H1N1 Subtype immunology, Lymphocytic choriomeningitis virus immunology
- Abstract
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., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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