Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor

Autores
Smulski, Cristian Roberto; Labovsky, Vivian; Levy, Gabriela Vanesa; Hontebeyrie, M.; Hoebeke, J.; Levin, Mariano Jorge
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
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
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
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
Fil: Hontebeyrie, M.. Instituto Pasteur; Francia
Fil: Hoebeke, J.. Centre National de la Recherche Scientifique; Francia
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
Materia
Protozoan Protein
Antibodies
Cross Reaction
Chagas Disease
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/28812
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/28812
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptorSmulski, Cristian RobertoLabovsky, VivianLevy, Gabriela VanesaHontebeyrie, M.Hoebeke, J.Levin, Mariano JorgeProtozoan ProteinAntibodiesCross ReactionChagas Diseasehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Antibodies 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.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; FranciaFil: 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; FranciaFil: 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; FranciaFil: Hontebeyrie, M.. Instituto Pasteur; FranciaFil: Hoebeke, J.. Centre National de la Recherche Scientifique; FranciaFil: 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; FranciaFederation of American Societies for Experimental Biology2006info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/28812Smulski, 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; 1396-14060892-66381530-6860CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/20/9/1396.shortinfo:eu-repo/semantics/altIdentifier/doi/10.1096/fj.05-5699cominfo:eu-repo/semantics/altIdentifier/pmid/16816115info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:23:29Zoai:ri.conicet.gov.ar:11336/28812instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:23:29.77CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
title Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
spellingShingle Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
Smulski, Cristian Roberto
Protozoan Protein
Antibodies
Cross Reaction
Chagas Disease
title_short Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
title_full Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
title_fullStr Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
title_full_unstemmed Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
title_sort Structural basis of the cross-reaction between an antibody to the Trypanosoma cruzi ribosomal P2beta protein and the human beta1 adrenergic receptor
dc.creator.none.fl_str_mv Smulski, Cristian Roberto
Labovsky, Vivian
Levy, Gabriela Vanesa
Hontebeyrie, M.
Hoebeke, J.
Levin, Mariano Jorge
author Smulski, Cristian Roberto
author_facet Smulski, Cristian Roberto
Labovsky, Vivian
Levy, Gabriela Vanesa
Hontebeyrie, M.
Hoebeke, J.
Levin, Mariano Jorge
author_role author
author2 Labovsky, Vivian
Levy, Gabriela Vanesa
Hontebeyrie, M.
Hoebeke, J.
Levin, Mariano Jorge
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Protozoan Protein
Antibodies
Cross Reaction
Chagas Disease
topic Protozoan Protein
Antibodies
Cross Reaction
Chagas Disease
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
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
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
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
Fil: Hontebeyrie, M.. Instituto Pasteur; Francia
Fil: Hoebeke, J.. Centre National de la Recherche Scientifique; Francia
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
description 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.
publishDate 2006
dc.date.none.fl_str_mv 2006
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/28812
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
0892-6638
1530-6860
CONICET Digital
CONICET
url http://hdl.handle.net/11336/28812
identifier_str_mv 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
0892-6638
1530-6860
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/20/9/1396.short
info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.05-5699com
info:eu-repo/semantics/altIdentifier/pmid/16816115
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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