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Science. 2014 Jan 17;343(6168):313-317. doi: 10.1126/science.1246829. Epub 2013 Dec 5.

Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.

Author information

1
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
2
Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
3
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
4
College of Pharmacy, Korea University, 339-700 Korea.
5
Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA 30322, USA.
6
Institut National de la Santéet de la Recherche Médicale U1013, Paris, France.
7
Université Paris Descartes, Sorbonne Paris Cité, Paris 75743 Paris Cedex 15, France.
8
Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30329, USA.
9
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
10
University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
#
Contributed equally

Abstract

The yellow fever vaccine YF-17D is one of the most successful vaccines ever developed in humans. Despite its efficacy and widespread use in more than 600 million people, the mechanisms by which it stimulates protective immunity remain poorly understood. Recent studies using systems biology approaches in humans have revealed that YF-17D-induced early expression of general control nonderepressible 2 kinase (GCN2) in the blood strongly correlates with the magnitude of the later CD8(+) T cell response. We demonstrate a key role for virus-induced GCN2 activation in programming dendritic cells to initiate autophagy and enhanced antigen presentation to both CD4(+) and CD8(+) T cells. These results reveal an unappreciated link between virus-induced integrated stress response in dendritic cells and the adaptive immune response.

PMID:
24310610
PMCID:
PMC4048998
DOI:
10.1126/science.1246829
[Indexed for MEDLINE]
Free PMC Article

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