Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities
| Autor: | Sibylle Tluk, Tanja Wader, Heather L. Davis, Jörg Vollmer, Meike Laucht, Ming Liu, Paul J. Payette, Risini D. Weeratna, Arthur M. Krieg, Christian Schetter, Marion Jurk |
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| Rok vydání: | 2004 |
| Předmět: |
CpG Oligodeoxynucleotide
medicine.medical_treatment Immunology Receptors Cell Surface Biology Mice In vivo Splenocyte medicine Animals Humans Immunology and Allergy B cell B-Lymphocytes Membrane Glycoproteins Toll-Like Receptors NF-kappa B Interferon-alpha TLR9 hemic and immune systems respiratory system Molecular biology Toll-Like Receptor 9 Cytokine medicine.anatomical_structure Oligodeoxyribonucleotides CpG site |
| Zdroj: | European Journal of Immunology. 34:251-262 |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | Oligodeoxynucleotides (ODN) with unmethylated deoxycytidyl-deoxyguanosine (CpG) dinucleotides (CpG ODN) mimic the immunostimulatory activity of bacterial DNA and are recognized by the Toll-like receptor 9 (TLR9). CpG ODN of the B-Class stimulate strong B cell and NK cell activation and cytokine production. The highest degrees of NK stimulation as well as IFN-alpha secretion by plasmacytoid DC were found to occur only with A-Class ODN. A third class of CpG ODN combines the immune effects of A- and B-Class CpG ODN. C-Class ODN strongly stimulate B cell or NK cell activation and IFN-alpha production. In contrast to the A-Class, the C-Class is wholly phosphorothioate, has no poly-G stretches, but has palindromic sequences combined with stimulatory CpG motifs. All classes stimulate TLR9-dependent signaling, but with strikingly different dose-response relationships that are quite in contrast to those observed for IFN-alpha. Effects similar to those on human cells were observed on mouse splenocytes. In contrast, splenocytes from TLR9-deficient mice did not show any response to the three CpG ODN classes. In vivo studies demonstrate that C-Class ODN are very potent Th1 adjuvants. C-Class ODN may represent new therapeutic drugs that combine the effects of A- and B-Class ODN for broad applications in infectious disease or cancer therapy. |
| Databáze: | OpenAIRE |
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