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 understand the mechanisms of intramuscular (i. m.) genetic immunization. Since myocytes are facultative antigen-presenting cells lacking MHC class II and co-stimulatory molecules, it was assumed that their unique role upon DNA vaccination is to synthesize and secrete the protein encoded by the plasmid. Here we describe that i. m. injection of unmethylated CpG motifs induced the expression of chemokines (monocyte chemotactic protein-1) and MHC class II molecules on myocytes. Our results indicate that immunostimulatory DNA sequences (CpG motifs) of DNA vaccines augment synthesis of chemokine by myocytes with subsequent recruitment of inflammatory cells secreting IFN-gamma, a potent cytokine that up-regulates the expression of MHC class II molecules on myocytes. A myoblast cell line triple transfected with plasmids encoding MHC class II molecules and an immunodominant CD4 T cell epitope of influenza virus presented the endogenously synthesized peptide and activated specific 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.
Stan
A C
AC
Department of Microbiology, Mount Sinai School of Medicine, New York, USA.
Casares
S
S
Brumeanu
T D
TD
Klinman
D M
DM
Bona
C A
CA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D018925:Chemokines / Q000096:biosynthesis*; D015226:Dinucleoside Phosphates / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000502:physiology; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D019444:Vaccines, DNA / Q000276:immunology*
D018925:Chemokines; D015226:Dinucleoside Phosphates; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D019444:Vaccines, DNA; C024138:I-E-antigen; C015772:CpG dinucleotide