Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs

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Date

2001-02-15

Author

Verthelyi, D
Ishii, KJ
Gürsel, Mayda
Takeshita, F
Klinman, DM

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Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of motifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurally distinct "clusters" of immunostimulatory CpG ODN, One cluster ("D") preferentially stimulates IFN-gamma production by NK cells, whereas the other ("K") stimulates cell proliferation and the production of IL-6 and IgM by monocytes and B cells. The distinct immunostimulatory properties of K and D ODN can improve the design of CpG-based products to achieve specific: therapeutic goals.

Subject Keywords

Immunology

URI

https://hdl.handle.net/11511/41573

Journal

JOURNAL OF IMMUNOLOGY

DOI

https://doi.org/10.4049/jimmunol.166.4.2372

Collections

Department of Biology, Article

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Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling. Shirota, H; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2004-10-15) Repetitive TTAGGG motifs present at high frequency in mammalian telomeres can suppress Th1-mediated immune responses. Synthetic oligonucleotides (ODN) containing TTAGGG motifs mimic this activity and have proven effective in the prevention/ treatment of certain Th1-dependent autoimmune diseases. This work explores the mechanism by which suppressive ODN block the induction of Th1 immunity. Findings indicate that these ODN inhibit IFN- -induced STAT1 phosphorylation and IL-12- induced STAT3 and STAT4 phosphor...
Cutting edge: Role of toll-like receptor 9 in CpG DNA-induced activation of human cells Takeshita, F; Leifer, CA; Gursel, I; Ishii, KJ; Takeshita, S; Gürsel, Mayda; Klinman, DM (The American Association of Immunologists, 2001-10-01) Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines and PBMC that recognize CpG DNA express membrane-bound human Toll-like receptor 9 (hTLR9). Cells that are not responsive to CpG DNA become responsive when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake of CpG (but not control) DNA into endocytic vesicles. Upon cell stimulation, hTLR9 and CpG DNA are found in the same endocytic vesicles. Cells expressing hTLR9 are ...
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation. Gursel, I; Gürsel, Mayda; Yamada, H; Ishii, KJ; Takeshita, F; Klinman, DM (The American Association of Immunologists, 2003-08-01) Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-te...
Effect of suppressive DNA on CpG-induced immune activation. Yamada, H; Gursel, I; Takeshita, F; Conover, J; Ishii, KJ; Gürsel, Mayda; Takeshita, S; Klinman, DM (The American Association of Immunologists, 2002-11-15) Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimula...

Citation Formats

D. Verthelyi, K. Ishii, M. Gürsel, F. Takeshita, and D. Klinman, “Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs,” JOURNAL OF IMMUNOLOGY, pp. 2372–2377, 2001, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/41573.