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Cell Rep ; 15(5): 1076-1087, 2016 05 03.
Article in English | MEDLINE | ID: mdl-27117419

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.


Subject(s)
Autophagy-Related Protein 5/genetics , Autophagy-Related Protein 7/genetics , Autophagy/immunology , CD8-Positive T-Lymphocytes/immunology , Dendritic Cells/immunology , Histocompatibility Antigens Class I/immunology , Influenza A Virus, H1N1 Subtype/immunology , Lymphocytic choriomeningitis virus/immunology , 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
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