The question of which dendritic cells (DCs) respond to pulmonary antigens and cross-prime CD8 + T cells remains controversial. We show here that influenza-specific CD8 + T cell priming was controlled by different DCs at different times after infection. Whereas early priming was controlled by both CD103+ CD11blo and CD103 CD11bhi DCs, CD103 CD11b hi DCs dominated antigen presentation at the peak of infection. Moreover, CD103 CD11b hi DCs captured exogenous antigens in the lungs and directly cross-primed CD8+ T cells in the draining lymph nodes without transferring antigen to CD8α+ DCs. Finally, we show that CD103 CD11b hi DCs were the only DCs to express CD70 after influenza infection and that CD70 expression on CD103 CD11b hi DCs licensed them to expand CD8 + T cell populations responding to both influenza and exogenous ovalbumin. © 2010 Nature America, Inc. All rights reserved.