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

• DOI: 10.1126/science.1246829
• Publication Date: 2013-12-06T02:34:15Z
• 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
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; Antigen Presentation; Yellow Fever Vaccine; Dendritic Cells; CD8-Positive T-Lymphocytes; Protein Serine-Threonine Kinases; Autophagy-Related Protein 7; Mice, Mutant Strains; Autophagy-Related Protein 5; Cell Line; 3. Good health; Enzyme Activation; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cricetinae; Animals; Humans; Microtubule-Associated Proteins

The Secret Life of a Vaccine

Antigen-specific CD8 ÷ T cells play a central role in the adaptive immune response to viral infections and to cancer.

Ravindran et al.

(p. 313 , published online 5 December) studied the successful yellow fever virus vaccine YF-17D to gain insight into its mechanism of action. The vaccine activated the nutrient deprivation sensor, GCN2 kinase, in dendritic cells. In transgenic mouse models, GCN2 activation promoted autophagy and antigen cross-presentation, enhancing the virus-specific CD8 ÷ T cell response. The findings suggest an important role for nutrient availability and autophagy in vaccine efficacy, which could aid more successful vaccine development.