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

The yellow fever vaccine YF-17D is one of the most successful vaccines ever developed in humans. Despite its efficacy and widespread use in over 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 GCN2 in the blood strongly correlates with the magnitude of the later CD8 + T cell response. Here 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.