Three surface molecules of mouse CD8+ dendritic cells (DCs), also found on the equivalent human DC subpopulation, were compared as targets for Ab-mediated delivery of Ags, a developing strategy for vaccination. For the production of cytotoxic T cells, DEC-205 and Clec9A, but not Clec12A, were effective targets, although only in the presence of adjuvants. For Ab production, however, Clec9A excelled as a target, even in the absence of adjuvant. Potent humoral immunity was a result of the highly specific expression of Clec9A on DCs, which allowed longer residence of targeting abs in the bloodstream, prolonged dc ag presentation, and extended cd4 t cell proliferation, all of which drove highly efficient development of follicular helper t cells. Because clec9a shows a similar expression pattern on human dcs, it has particular promise as a target for vaccines of human application.