Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions

Summary Host defense against viruses and intracellular parasites depends on effector CD8 + T cells, whose optimal clonal expansion, differentiation, and memory properties require signals from CD4 + T cells. Here, we addressed the role of dendritic cell (DC) subsets in initial activation of the two T cell types and their co-operation. Surprisingly, initial priming of CD4 + and CD8 + T cells was spatially segregated within the lymph node and occurred on different DCs with temporally distinct patterns of antigen presentation via MHCI versus MHCII molecules. DCs that co-present antigen via both MHC molecules were detected at a later stage; these XCR1 + DCs are the critical platform involved in CD4 + T cell augmentation of CD8 + T cell responses. These findings delineate the complex choreography of cellular interactions underlying effective cell-mediated anti-viral responses, with implications for basic DC subset biology, as well as for translational application to the development of vaccines that evoke optimal T cell immunity.