To understand how adaptive immune responses are generated against bacteria that avoid being delivered to lysosomes, interactions between professional antigen-presenting cells (APCs) and the intracellular pathogen Legionella pneumophila were examined. In contrast to murine bone marrow-derived macrophages (BMMs), we show that dendritic cells (DCs) restrict the growth of intracellular Legionella. Similar to what has been reported in BMMs, phagosomes containing Legionella matured into endoplasmic reticulum (ER)-derived organelles after DC internalization. Biogenesis of an ER-derived vacuole did not effectively sequester Legionella antigens from presentation on MHC class II molecules (MHC II). It was determined that proteins synthesized after Legionella had established residence in an ER-derived vacuole were presented by infected APCs. These data indicate that the ability of DCs to restrict intracellular growth of Legionella could be an important property that facilitates priming of protective T cell-mediated immune responses to vacuolar pathogens.