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

Rajesh Ravindran | Zendy; Nooruddin Khan | Zendy; Helder I. Nakaya | Zendy; Shuzhao Li | Zendy; Jens Loebbermann | Zendy; Mohan S. Maddur | Zendy; Youngja Park | Zendy; Dean P. Jones | Zendy; Pascal Chappert | Zendy; Jean Davoust | Zendy; David S. Weiss | Zendy; Herbert W. Virgin | Zendy; David Ron | Zendy; Bali Pulendran | Zendy

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

Author(s) -

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

Publication year - 2013

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1246829

Subject(s) - immune system , antigen presentation , cross presentation , autophagy , biology , antigen , dendritic cell , virology , acquired immune system , cd8 , cytotoxic t cell , t cell , virus , immunity , immunology , microbiology and biotechnology , biochemistry , apoptosis , in vitro

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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