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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Autor principal:	Elías, Fernanda
Publicado:	2003
Materias:	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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n7_p3697_Elias http://hdl.handle.net/20.500.12110/paper_00221767_v171_n7_p3697_Elias
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_00221767_v171_n7_p3697_Elias2023-06-08T14:46:55Z Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs Elías, Fernanda 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. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n7_p3697_Elias 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 Elías, Fernanda 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.
author	Elías, Fernanda
author_facet	Elías, Fernanda
author_sort	Elías, Fernanda
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
publishDate	2003
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n7_p3697_Elias http://hdl.handle.net/20.500.12110/paper_00221767_v171_n7_p3697_Elias
work_keys_str_mv	AT eliasfernanda strongcytosineguanosineindependentimmunostimulationinhumansandotherprimatesbysyntheticoligodeoxynucleotideswithpynttttgtmotifs
_version_	1768546615497326592

Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs

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