Macroautophagy Proteins Control MHC Class I Levels on Dendritic Cells and Shape Anti-viral CD8+ T Cell Responses

• Atg5- and 7-deficient dendritic cells (DCs) have increased surface MHC class I levels
• MHC class I internalization is compromised in the absence of Atg5
• In the absence of LC3 lipidation, AAK1 gets less efficiently recruited to MHC class I
• As a result, anti-viral CD8+ T cell responses are more efficiently stimulated

SummaryThe 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.

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