The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA

DNA-based vaccines generate potent CTL responses. The mechanism of T cell s timulation has been attributed to plasmid-transfected dendritic cells. Thes e cells have also been shown to express plasmid-encoded proteins and to bec ome activated by surface marker up-regulatisn. However, the increased surfa ce expression of CD40 and B7 on these dendritic cells is insufficient to ov ercome the need for MHC class II-restricted CD4(+) T cell help in the primi ng of a CTL response. In this study, MHC class II-/- mice were unable to ge nerate a CTL response following DNA immunization. This deficit in CTL stimu lation by MHC class II-deficient mice was only modestly restored with CD40- activating Ab, suggesting that there were other elements provided by MHC cl ass II-restricted T cell help for CTL induction. CTL activity was also augm ented by coinjection with a vector encoding the costimulatory ligand B7.1, but not B7.2. These data indicate that dendritic cells in plasmid DNA-injec ted mice require conditioning signals from MHC class II-restricted T cells that are both CD40 dependent and independent and that there are different r oles for costimulatory molecules that may be involved in inducing optimal C TL activity.