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

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

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 languageEnglish
Pages (from-to)1076-1087
Number of pages12
JournalCell Reports
Volume15
Issue number5
DOIs
StatePublished - 3 May 2016

Keywords

  • AAK1
  • Endocytosis
  • Immune control
  • Influenza
  • LCMV

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