Strong Cytosine-Guanosine-Independent Immunostimulation in Humans and Other Primates by Synthetic Oligodeoxynucleotides with PyNTTTTGT Motifs
| Autor: | Alejandro D. Montaner, Fernanda Elías, Juan M. Rodríguez, Ricardo A. López, Jorge Zorzopulos, Juan Fló |
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| Rok vydání: | 2003 |
| Předmět: |
Cell division
Swine medicine.drug_class Antigens CD19 Immunology B-Lymphocyte Subsets Guanosine Stimulation Regulatory Sequences Nucleic Acid Biology Lymphocyte Activation Immunostimulant chemistry.chemical_compound Adjuvants Immunologic Species Specificity medicine Animals Humans Immunology and Allergy CD40 Antigens Sheep Interleukin-6 Histocompatibility Antigens Class I Histocompatibility Antigens Class II hemic and immune systems Dendritic Cells Haplorhini Thionucleotides respiratory system biology.organism_classification Oligodeoxyribonucleotides chemistry Biochemistry CpG site Phosphodiester bond Leukocytes Mononuclear CpG Islands Cell Division Cytosine |
| Zdroj: | The Journal of Immunology. 171:3697-3704 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Synthetic oligodeoxynucleotides (ODNs) containing cytosine-guanosine (CpG) motifs stimulate B and plasmacytoid dendritic cells of the vertebrate immune system. We found that in primates strong stimulation of these cells could also be achieved using certain non-CpG ODNs. The immunostimulatory motif in this case is a sequence with the general formula PyNTTTTGT in which Py is C or T, and N is A, T, C, or G. Assays performed on purified cells indicated that the immunostimulatory activity is direct. The use of a nuclease-resistant phosphorothioate backbone is not a necessary condition, since phosphodiester PyNTTTTGT ODNs are active. It was also demonstrated that ODN 2006, a widely used immunostimulant of human B cells, possess two kinds of immunostimulatory motifs: one of them mainly composed of two successive TCG trinucleotides located at the 5′ end and another one (duplicated) of the PyNTTTTGT kind here described. Even though PyNTTTTGT ODNs are mainly active on primate cells, some of them, bearing the CATTTTGT motif, have a small effect on cells from other mammals. This suggests that the immunostimulatory mechanism activated by these ODNs was present before, but optimized during, evolution of primates. Significant differences in the frequency of PyNTTTTGT sequences between bacterial and human DNA were not found. Thus, the possibility that PyNTTTTGT ODNs represent a class of pathogen-associated molecular pattern is unlikely. They could, more reasonably, be included within the category of danger signals of cell injury. |
| Databáze: | OpenAIRE |
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