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

TitleVaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.
Publication TypeJournal Article
Year of Publication2014
AuthorsRavindran R, Khan N, Nakaya HI, Li S, Loebbermann J, Maddur MS, Park Y, Jones DP, Chappert P, Davoust J, Weiss DS, Virgin HW, Ron D, Pulendran B
JournalScience
Volume343
Issue6168
Pagination313-7
Date Published01/2014
ISSN1095-9203
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.

DOI10.1126/science.1246829
Alternate JournalScience
PubMed ID24310610
Grant List084812/Z/08/Z / / Wellcome Trust / United Kingdom
N01 AI50019 / AI / NIAID NIH HHS / United States
N01 AI50025 / AI / NIAID NIH HHS / United States
R37 AI048638 / AI / NIAID NIH HHS / United States
R37 DK057665 / DK / NIDDK NIH HHS / United States
U19 AI057266 / AI / NIAID NIH HHS / United States
U19 AI090023 / AI / NIAID NIH HHS / United States
U54 AI057157 / AI / NIAID NIH HHS / United States
U54 AI057160 / AI / NIAID NIH HHS / United States
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