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Abstract:

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.

Registro:

Documento: Artículo
Título:Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs
Autor:Elias, F.; Flo, J.; Lopez, R.A.; Zorzopulos, J.; Montaner, A.; Rodriguez, J.M.
Filiación:Departamento de Quimica Biologica, Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Immunotech S.A., Buenos Aires, Argentina
Inst. de Investigaciones Biomedicas, Fundacion Pablo Cassara, Buenos Aires, Argentina
Inst. de Investigaciones Biomedicas, Fundacion Pablo. Cassara, Saladillo 2452, Buenos Aires 1440, Argentina
Palabras clave: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
Año:2003
Volumen:171
Número:7
Página de inicio:3697
Página de fin:3704
DOI: http://dx.doi.org/10.4049/jimmunol.171.7.3697
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
ISSN:00221767
CODEN:JOIMA
CAS:adenosine, 58-61-7; cytosine, 71-30-7; guanosine, 118-00-3; nuclease, 9026-81-7; phosphorothioic acid, 10101-88-9, 13598-51-1, 15181-41-6; thymidine, 50-89-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v171_n7_p3697_Elias

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Citas:

---------- APA ----------
Elias, F., Flo, J., Lopez, R.A., Zorzopulos, J., Montaner, A. & Rodriguez, J.M. (2003) . Strong cytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs. Journal of Immunology, 171(7), 3697-3704.
http://dx.doi.org/10.4049/jimmunol.171.7.3697
---------- CHICAGO ----------
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" . Journal of Immunology 171, no. 7 (2003) : 3697-3704.
http://dx.doi.org/10.4049/jimmunol.171.7.3697
---------- MLA ----------
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" . Journal of Immunology, vol. 171, no. 7, 2003, pp. 3697-3704.
http://dx.doi.org/10.4049/jimmunol.171.7.3697
---------- VANCOUVER ----------
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. J. Immunol. 2003;171(7):3697-3704.
http://dx.doi.org/10.4049/jimmunol.171.7.3697