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 together, synergistically promoted the Ag-specific Th1 development and inhibited the Th2-mediated airway eosinophilia. In this study, we examined the mechanisms 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 OVA, but mirrored the augmented binding of the CpG-tagged Ag to dendritic cells (DCs) in a CpG-guided manner, because phycobiliprotein, R-PE, conjugated 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 properties as promoters of Ag uptake and DC activators, thereby potentiating the ability of DCs to generate Th1 cells. The DNA-mediated promotion of Ag uptake would be advantageous for evoking host immune responses against invading microorganisms.
Shirota
H
H
First Department of Internal Medicine and Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan.
Sano
K
K
Hirasawa
N
N
Terui
T
T
Ohuchi
K
K
Hattori
T
T
Shirato
K
K
Tamura
G
G
D000276:Adjuvants, Immunologic / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D006133:Growth Substances / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D045342:Light-Harvesting Protein Complexes; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D006133:Growth Substances; D045342:Light-Harvesting Protein Complexes; C111390:OVA 323-339; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D010940:Plant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin