Novel roles of CpG oligodeoxynucleotides as a leader for the sampling and presentation of CpG-tagged antigen by dendritic cells

Oligodeoxynucleotides containing CpG motifs have been highlighted as potent Th1 activators. We previously reported that Ag and CpG, when conjugated to gether, synergistically promoted the Ag-specific Th1 development and inhibi ted the Th2-mediated airway eosinophilia. In this study, we examined the me chanisms underlying the synergism of the covalent conjugation. The CpG-OVA conjugate enhanced the Th1 activation and development. These characteristic features of the conjugate could not be ascribed to the polymerization of O VA, but mirrored the augmented binding of the CpG-tagged Ag to dendritic ce lls (DCs) in a CpG-guided manner, because phycobiliprotein, R-PE, conjugate d to CpG stained a higher proportion of DCs with higher intensity than the mixture. R-PE fluorescence was emitted from cytoplasmic portions of the DCs , which simultaneously expressed costimulatory molecules and IL-12. The CpG -conjugated R-PE trafficking described above actually served as a potent Ag . These results indicate that CpG conjugated to Ag exhibit novel joint prop erties as promoters of Ag uptake and DC activators, thereby potentiating th e ability of DCs to generate Th1 cells. The DNA-mediated promotion of Ag up take would be advantageous for evoking host immune responses against invadi ng microorganisms.