Memory CD8+ Tcells are programmed during the primary response for robust secondary responsiveness. Here we show that CD8+ Tcells responding todifferent epitopes of influenza virus received qualitatively different signals during the primary response that altered their secondary responsiveness. Nucleoprotein (NP)-specific CD8+ Tcells encountered antigen on CD40-licensed, CD70-expressing, CD103-CD11bhi dendritic cells (DCs) at later times in the primary response. As a consequence, they maintained CD25 expression and responded to interleukin-2 (IL-2) and CD27, which together programmed their robust secondary proliferative capacity and interferon-γ (IFN-γ)-producing ability. In contrast, polymerase (PA)-specific CD8+ Tcells did not encounter antigen-bearing, CD40-activated DCs at later times in the primary response, did not receive CD27 and CD25 signals, and were not programmed to become memory CD8+ Tcells with strong proliferative and cytokine-producing ability. As a result, CD8+ Tcells responding to abundant antigens, like NP, dominated the secondary response. © 2014 Elsevier Inc.
