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dc.contributor.author
Smulski, Cristian Roberto
dc.contributor.author
Labovsky, Vivian
dc.contributor.author
Levy, Gabriela Vanesa
dc.contributor.author
Hontebeyrie, M.
dc.contributor.author
Hoebeke, J.
dc.contributor.author
Levin, Mariano Jorge
dc.date.available
2017-11-23T13:09:24Z
dc.date.issued
2006
dc.identifier.citation
Smulski, Cristian Roberto; Labovsky, Vivian; Levy, Gabriela Vanesa; Hontebeyrie, M.; Hoebeke, J.; et al.; Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor; Federation of American Societies for Experimental Biology; FASEB Journal; 20; 9; -1-2006; 1396-1406
dc.identifier.issn
0892-6638
dc.identifier.uri
http://hdl.handle.net/11336/28812
dc.description.abstract
Antibodies from patients with Chagas heart disease and monoclonal antibodies (or mAb) to the carboxy-terminal end (B cell epitope R13) of the ribosomal P2beta protein of Trypanosoma cruzi (TcP2beta) cross-react with the beta1 adrenergic receptor (beta1-AR). Two single-chain Fv fragments (scFv) C5 and B7 derived from the variable regions of the anti-R13 mAb 17.2 were expressed. scFv C5 was a dimer and bound to TcP2beta with an affinity of K(d) = 8 nM, whereas scFv B7 was monomeric and had less affinity than scFv C5 for TcP2beta, K(d) = 46 nM. The affinity constant of scFv C5 to the second extracellular loop of the human beta1-AR was of 10 microM. Moreover, scFv C5 induced an increase in cAMP levels of CHO-K cells transfected with the human beta1-AR; scFv B7 had no effect but blocked isoproterenol stimulation. The agonist-like activity of scFv C5 and the antagonist activity of scFv B7 were both confirmed in vivo on heart beating frequency after their passive transfer to mice. Molecular modeling of the variable region of mAb 17.2 indicated which amino acids were likely to be involved in recognizing both peptide EDDDMGFGLF, derived from the R13 epitope of TcP2beta, and peptide ESDEARRCYN from the second extracellular loop of the human beta1-AR. It is plausible that the recently described cross-reaction of mAb 17.2 with rhodopsin can also be explained by this model. The physiological effects of this type of anti-T. cruzi antibodies may increase the liability of patients with Chagas disease.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Federation of American Societies for Experimental Biology
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Protozoan Protein
dc.subject
Antibodies
dc.subject
Cross Reaction
dc.subject
Chagas Disease
dc.subject.classification
Virología
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-10-26T14:50:29Z
dc.identifier.eissn
1530-6860
dc.journal.volume
20
dc.journal.number
9
dc.journal.pagination
1396-1406
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Smulski, Cristian Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Instituto Pasteur; Francia
dc.description.fil
Fil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Instituto Pasteur; Francia
dc.description.fil
Fil: Levy, Gabriela Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Instituto Pasteur; Francia
dc.description.fil
Fil: Hontebeyrie, M.. Instituto Pasteur; Francia
dc.description.fil
Fil: Hoebeke, J.. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Levin, Mariano Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Inserm; Francia
dc.journal.title
FASEB Journal
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/20/9/1396.short
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1096/fj.05-5699com
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/pmid/16816115


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