What are the mechanisms of immunity following DNA vaccination?
The efficiency of DNA vaccination depends on the interaction among genetic material, lymphocytes, and APCs. Following intramuscular injection, myocytes play the role of antigen factories. They primarily express MHC class I and under certain circumstances express MHC class II; however, they do not express the costimulatory molecules required for priming and activation of T cells and thus lack function as effective APCs (1). Alternatively, small numbers of bone marrow–derived DCs and other professional APCs that can be activated to express high levels of MHC, as well as costimulatory molecules, are present at the site of injection and become transfected with the injected DNA. Cross-priming may occur, in which CD8+ T cell responses are primed by exogenous class I–restricted peptides that are not expressed in, but rather are acquired by, local APCs (2, 3). Regardless of the underlying mechanism, it has become clear that in the context of DNA vaccination APCs are key inducers of immunity, a