CpG motifs of DNA vaccines induce the expression of chemokines and MHC class II molecules on myocytes

Determining how an immune response is initiated after in vivo transfection of myocytes with plasmids encoding foreign antigens is essential to underst and the mechanisms of intramuscular (i.m.) genetic immunization. Since myoc ytes are facultative antigen-presenting cells lacking MHC class II and co-s timulatory molecules, it was assumed that their unique role upon DNA vaccin ation is to synthesize and secrete the protein encoded by the plasmid. Here we describe that i.m. injection of unmethylated CpG motifs induced the exp ression of chemokines (monocyte chemotactic protein-1) and MHC class II mol ecules on myocytes. Our results indicate that immunostimulatory DNA sequenc es (CpG motifs) of DNA vaccines augment synthesis of chemokine by myocytes with subsequent recruitment of inflammatory cells secreting IFN-gamma, a po tent cytokine that up-regulates the expression of MHC class II molecules on myocytes. A myoblast cell line triple transfected with plasmids encoding M HC class II molecules and an immunodominant CD4 T cell epitope of influenza virus presented the endogenously synthesized peptide and activated specifi c T cells. These findings suggest that one mechanism for the immunogenicity of DNA vaccines consists in the presentation of peptides to CD4 T cells by in vivo plasmid-transfected myocytes.