Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs
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 i...
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todo:paper_00221767_v171_n7_p3697_Elias2023-10-03T14:27:54Z Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs Elias, F. Flo, J. Lopez, R.A. Zorzopulos, J. Montaner, A. Rodriguez, J.M. adenosine bacterial DNA cytosine guanosine nuclease oligonucleotide phosphorothioic acid thymidine animal cell article B lymphocyte cell damage cell stimulation controlled study dendritic cell human human cell immune system immunostimulation nonhuman nucleotide sequence primate priority journal protein motif vertebrate 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. Fil:Elias, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221767_v171_n7_p3697_Elias |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
adenosine bacterial DNA cytosine guanosine nuclease oligonucleotide phosphorothioic acid thymidine animal cell article B lymphocyte cell damage cell stimulation controlled study dendritic cell human human cell immune system immunostimulation nonhuman nucleotide sequence primate priority journal protein motif vertebrate |
| spellingShingle |
adenosine bacterial DNA cytosine guanosine nuclease oligonucleotide phosphorothioic acid thymidine animal cell article B lymphocyte cell damage cell stimulation controlled study dendritic cell human human cell immune system immunostimulation nonhuman nucleotide sequence primate priority journal protein motif vertebrate Elias, F. Flo, J. Lopez, R.A. Zorzopulos, J. Montaner, A. Rodriguez, J.M. Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs |
| topic_facet |
adenosine bacterial DNA cytosine guanosine nuclease oligonucleotide phosphorothioic acid thymidine animal cell article B lymphocyte cell damage cell stimulation controlled study dendritic cell human human cell immune system immunostimulation nonhuman nucleotide sequence primate priority journal protein motif vertebrate |
| description |
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. |
| format |
JOUR |
| author |
Elias, F. Flo, J. Lopez, R.A. Zorzopulos, J. Montaner, A. Rodriguez, J.M. |
| author_facet |
Elias, F. Flo, J. Lopez, R.A. Zorzopulos, J. Montaner, A. Rodriguez, J.M. |
| author_sort |
Elias, F. |
| title |
Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs |
| title_short |
Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs |
| title_full |
Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs |
| title_fullStr |
Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs |
| title_full_unstemmed |
Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs |
| title_sort |
strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with pynttttgt motifs |
| url |
http://hdl.handle.net/20.500.12110/paper_00221767_v171_n7_p3697_Elias |
| work_keys_str_mv |
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1807318593033994240 |