Vaccine Activation of the Nutrient Sensor GCN2 in Dendritic Cells Enhances Antigen Presentation

Overview

Journal Science

Specialty Science

Date 2013 Dec 7

PMID 24310610

Citations 118

Authors

Rajesh Ravindran

Nooruddin Khan

Helder I Nakaya

Shuzhao Li

Jens Loebbermann

Mohan S Maddur

Youngja Park

Dean P Jones

Pascal Chappert

Jean Davoust

David S Weiss

Herbert W Virgin

David Ron

Bali Pulendran

Affiliations

Soon will be listed here.

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.

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