DNA vaccines can stimulate both humoral and cytolytic immune responses, Alt
hough bone marrow-derived elements present the expressed rig, the mechanism
s for acquiring immunogenic peptides have yet to be fully elucidated, APCs
may become directly transfected by plasmid DNA or process extracellular pro
teins produced by other transfected cells. Using a transactivating plasmid
system and bone marrow chimeras, we show that both mechanisms appear to be
involved however, the bulk of the immune response is dependent on expressio
n of Ag by nonlymphoid tissues and transfer to APCs. These in vivo studies
are the first to define the role of transfected nonlymphoid cells in genera
ting Ag for presentation by bone marrow-derived APCs after needle injection
with plasmid DNA.