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. Macroautophagy assists in antigen processing for MHC class II presentation. In contrast to this supportive role for CD4+ T cell stimulation, Loi et al. demonstrate that macroautophagy proteins diminish antigen presentation on MHC class I molecules during anti-viral CD8+ T cell responses by supporting MHC class I internalization in dendritic cells.
Original language | English |
---|---|
Pages (from-to) | 1076-1087 |
Number of pages | 12 |
Journal | Cell Reports |
Volume | 15 |
Issue number | 5 |
DOIs | |
State | Published - 3 May 2016 |
Keywords
- AAK1
- Endocytosis
- Immune control
- Influenza
- LCMV