Oligodeoxynucleotides without CpG motifs work as adjuvant for the induction of Th2 differentiation in a sequence-independent manner.
The outcomes of immune responses are regulated by various parameters including how Ags are handled by APCs. In this study, we describe the intrinsic immunomodulatory characteristics of oligodeoxynucleotides (ODNs) that improve the Ag presentation by APCs. ODNs (20-mer) containing CpG motifs induced strong Th1-skewed responses. In contrast, those without CpG motifs enhanced cytokine production by effector Th cells without particular skewing toward Th1 responses or induced the differentiation of unprimed CD4(+) T cells toward Th2 cells. These functional features were prominently envisaged when ODNs were conjugated to the Ag, and were underlain by the facilitated binding of ODN-conjugated Ag to Ia(+) cells. Despite the functional differences between ODNs with CpG motifs and those without CpG motifs, both ODNs bound to Ia(+) cells with similar affinity and kinetics. Immunoenhancing activities of the ODNs were not sequence-dependent; the characteristics, including the facilitation of Ag capture, enhancement of effector Th cell responses, and induction of Th2 cells, were shared by randomly synthesized ODNs conjugated to Ag. This is the first study suggesting that ODNs, independent of the sequences, enhance immune responses through the promoted capture of ODN-conjugated Ag by APCs.
Sano
Kunio
K
Department of Respiratory and Infectious Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan. sano@int1.med.tohoku.ac.jp
Shirota
Hidekazu
H
Terui
Tadashi
T
Hattori
Toshio
T
Tamura
Gen
G
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004705:Endocytosis / Q000276:immunology; D005456:Fluorescent Dyes / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9
D000276:Adjuvants, Immunologic; D000941:Antigens; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010714:Phosphatidylethanolamines; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C042077:N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phosphatidylethanolamine; D010047:Ovalbumin