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Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells

Abstract : Cross-presentation of cell-associated antigen is important in the priming of CD8(+) T-cell responses to proteins that are not expressed by antigen-presenting cells (APCs). In vivo, dendritic cells are the main cross-presenting APC, and much is known regarding their ability to capture and process cell-associated antigen. In contrast, little is known about the way death effector pathways influence the efficiency of cross-priming. Here, we compared two important mechanisms of programmed cell death: classical apoptosis, as it occurs in wild-type (WT) fibroblasts, and caspase-independent cell death, which occurs with increased features of autophagy in Bax/Bak(-/-) fibroblasts. We assessed virally infected WT and Bax/Bak(-/-) fibroblasts as a source of cell-associated antigen. We found that immunization with cells undergoing autophagy before cell death was superior in facilitating the cross-priming of antigen-specific CD8(+) T cells. Strikingly, silencing of Atg5 expression inhibited priming. We interpret this to be a novel form of 'immunogenic death' with the enhanced priming efficiency being a result of persistent MHC I cross-presentation and the induction of type I interferons. These results offer the first molecular evidence that catabolic pathways, including autophagy, influence the efficiency of cross-priming. We predict that targeting the autophagy cascade may provide a therapeutic strategy for achieving robust cross-priming of viral and tumor-specific CD8(+) T cells.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01402288
Contributor : Marie-Christine Vougny <>
Submitted on : Thursday, November 24, 2016 - 2:54:44 PM
Last modification on : Wednesday, September 16, 2020 - 5:11:41 PM

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M Uhl, O Kepp, H Jusforgues-Saklani, J-M Vicencio, G Kroemer, et al.. Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8+ T cells. Cell Death and Differentiation, Nature Publishing Group, 2009, 16 (7), pp.991 - 1005. ⟨10.1038/cdd.2009.8⟩. ⟨pasteur-01402288⟩

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