Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein

Autores
Valiente Gabioud, Ariel Alejandro; Veaute, Carolina Melania Isabel; Perrig, Melina Soledad; Galan Romano, Félix S.; Sferco, Silvano Juan; Marcipar, Iván Sergio
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Repetitive proteins (RP) of Trypanosoma cruzi are highly present in the parasite and are strongly recognized by sera from Chagas' disease patients. Flagelar Repetitive Antigen (FRA), which is expressed in all steps of the parasite life cycle, is the RP that displays the greatest number of aminoacids per repeat and has been indicated as one of the most suitable candidate for diagnostic test because of its high performance in immunoassays. Here we analyzed the influence of the number of repeats on the immunogenic and antigenic properties of the antigen. Recombinant proteins containing one, two, and four tandem repeats of FRA (FRA1, FRA2, and FRA4, respectively) were obtained and the immune response induced by an equal amount of repeats was evaluated in a mouse model. The reactivity of specific antibodies present in sera from patients naturally infected with T. cruzi was also assessed against FRA1, FRA2, and FRA4 proteins, and the relative avidity was analyzed. We determined that the number of repeats did not increase the humoral response against the antigen and this result was reproduced when the repeated motifs were alone or fused to a non-repetitive protein. By contrast, the binding affinity of specific human antibodies increases with the number of repeated motifs in FRA antigen. We then concluded that the high ability of FRA to be recognized by specific antibodies from infected individuals is mainly due to a favorable polyvalent interaction between the antigen and the antibodies. In accordance with experimental results, a 3D model was proposed and B epitope in FRA1, FRA2, and FRA4 were predicted.
Fil: Valiente Gabioud, Ariel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Veaute, Carolina Melania Isabel. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Perrig, Melina Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Galan Romano, Félix S.. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Sferco, Silvano Juan. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Materia
American Trypanosomiasis
Antigen
Antigenicity
Immunogenicity
Repetitive Proteins
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:11336/74089
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/74089
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA proteinValiente Gabioud, Ariel AlejandroVeaute, Carolina Melania IsabelPerrig, Melina SoledadGalan Romano, Félix S.Sferco, Silvano JuanMarcipar, Iván SergioAmerican TrypanosomiasisAntigenAntigenicityImmunogenicityRepetitive Proteinshttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Repetitive proteins (RP) of Trypanosoma cruzi are highly present in the parasite and are strongly recognized by sera from Chagas' disease patients. Flagelar Repetitive Antigen (FRA), which is expressed in all steps of the parasite life cycle, is the RP that displays the greatest number of aminoacids per repeat and has been indicated as one of the most suitable candidate for diagnostic test because of its high performance in immunoassays. Here we analyzed the influence of the number of repeats on the immunogenic and antigenic properties of the antigen. Recombinant proteins containing one, two, and four tandem repeats of FRA (FRA1, FRA2, and FRA4, respectively) were obtained and the immune response induced by an equal amount of repeats was evaluated in a mouse model. The reactivity of specific antibodies present in sera from patients naturally infected with T. cruzi was also assessed against FRA1, FRA2, and FRA4 proteins, and the relative avidity was analyzed. We determined that the number of repeats did not increase the humoral response against the antigen and this result was reproduced when the repeated motifs were alone or fused to a non-repetitive protein. By contrast, the binding affinity of specific human antibodies increases with the number of repeated motifs in FRA antigen. We then concluded that the high ability of FRA to be recognized by specific antibodies from infected individuals is mainly due to a favorable polyvalent interaction between the antigen and the antibodies. In accordance with experimental results, a 3D model was proposed and B epitope in FRA1, FRA2, and FRA4 were predicted.Fil: Valiente Gabioud, Ariel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; ArgentinaFil: Veaute, Carolina Melania Isabel. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; ArgentinaFil: Perrig, Melina Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Galan Romano, Félix S.. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Sferco, Silvano Juan. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaAcademic Press Inc Elsevier Science2011-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/74089Valiente Gabioud, Ariel Alejandro; Veaute, Carolina Melania Isabel; Perrig, Melina Soledad; Galan Romano, Félix S.; Sferco, Silvano Juan; et al.; Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein; Academic Press Inc Elsevier Science; Experimental Parasitology; 127; 3; 3-2011; 672-6790014-4894CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/21118687info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2010.11.011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:21:26Zoai:ri.conicet.gov.ar:11336/74089instacron: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:34982025-09-10 13:21:26.422CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
title Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
spellingShingle Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
Valiente Gabioud, Ariel Alejandro
American Trypanosomiasis
Antigen
Antigenicity
Immunogenicity
Repetitive Proteins
title_short Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
title_full Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
title_fullStr Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
title_full_unstemmed Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
title_sort Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein
dc.creator.none.fl_str_mv Valiente Gabioud, Ariel Alejandro
Veaute, Carolina Melania Isabel
Perrig, Melina Soledad
Galan Romano, Félix S.
Sferco, Silvano Juan
Marcipar, Iván Sergio
author Valiente Gabioud, Ariel Alejandro
author_facet Valiente Gabioud, Ariel Alejandro
Veaute, Carolina Melania Isabel
Perrig, Melina Soledad
Galan Romano, Félix S.
Sferco, Silvano Juan
Marcipar, Iván Sergio
author_role author
author2 Veaute, Carolina Melania Isabel
Perrig, Melina Soledad
Galan Romano, Félix S.
Sferco, Silvano Juan
Marcipar, Iván Sergio
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv American Trypanosomiasis
Antigen
Antigenicity
Immunogenicity
Repetitive Proteins
topic American Trypanosomiasis
Antigen
Antigenicity
Immunogenicity
Repetitive Proteins
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Repetitive proteins (RP) of Trypanosoma cruzi are highly present in the parasite and are strongly recognized by sera from Chagas' disease patients. Flagelar Repetitive Antigen (FRA), which is expressed in all steps of the parasite life cycle, is the RP that displays the greatest number of aminoacids per repeat and has been indicated as one of the most suitable candidate for diagnostic test because of its high performance in immunoassays. Here we analyzed the influence of the number of repeats on the immunogenic and antigenic properties of the antigen. Recombinant proteins containing one, two, and four tandem repeats of FRA (FRA1, FRA2, and FRA4, respectively) were obtained and the immune response induced by an equal amount of repeats was evaluated in a mouse model. The reactivity of specific antibodies present in sera from patients naturally infected with T. cruzi was also assessed against FRA1, FRA2, and FRA4 proteins, and the relative avidity was analyzed. We determined that the number of repeats did not increase the humoral response against the antigen and this result was reproduced when the repeated motifs were alone or fused to a non-repetitive protein. By contrast, the binding affinity of specific human antibodies increases with the number of repeated motifs in FRA antigen. We then concluded that the high ability of FRA to be recognized by specific antibodies from infected individuals is mainly due to a favorable polyvalent interaction between the antigen and the antibodies. In accordance with experimental results, a 3D model was proposed and B epitope in FRA1, FRA2, and FRA4 were predicted.
Fil: Valiente Gabioud, Ariel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Veaute, Carolina Melania Isabel. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina
Fil: Perrig, Melina Soledad. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Galan Romano, Félix S.. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina
Fil: Sferco, Silvano Juan. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Marcipar, Iván Sergio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Tecnología Inmunológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
description Repetitive proteins (RP) of Trypanosoma cruzi are highly present in the parasite and are strongly recognized by sera from Chagas' disease patients. Flagelar Repetitive Antigen (FRA), which is expressed in all steps of the parasite life cycle, is the RP that displays the greatest number of aminoacids per repeat and has been indicated as one of the most suitable candidate for diagnostic test because of its high performance in immunoassays. Here we analyzed the influence of the number of repeats on the immunogenic and antigenic properties of the antigen. Recombinant proteins containing one, two, and four tandem repeats of FRA (FRA1, FRA2, and FRA4, respectively) were obtained and the immune response induced by an equal amount of repeats was evaluated in a mouse model. The reactivity of specific antibodies present in sera from patients naturally infected with T. cruzi was also assessed against FRA1, FRA2, and FRA4 proteins, and the relative avidity was analyzed. We determined that the number of repeats did not increase the humoral response against the antigen and this result was reproduced when the repeated motifs were alone or fused to a non-repetitive protein. By contrast, the binding affinity of specific human antibodies increases with the number of repeated motifs in FRA antigen. We then concluded that the high ability of FRA to be recognized by specific antibodies from infected individuals is mainly due to a favorable polyvalent interaction between the antigen and the antibodies. In accordance with experimental results, a 3D model was proposed and B epitope in FRA1, FRA2, and FRA4 were predicted.
publishDate 2011
dc.date.none.fl_str_mv 2011-03
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/11336/74089
Valiente Gabioud, Ariel Alejandro; Veaute, Carolina Melania Isabel; Perrig, Melina Soledad; Galan Romano, Félix S.; Sferco, Silvano Juan; et al.; Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein; Academic Press Inc Elsevier Science; Experimental Parasitology; 127; 3; 3-2011; 672-679
0014-4894
CONICET Digital
CONICET
url http://hdl.handle.net/11336/74089
identifier_str_mv Valiente Gabioud, Ariel Alejandro; Veaute, Carolina Melania Isabel; Perrig, Melina Soledad; Galan Romano, Félix S.; Sferco, Silvano Juan; et al.; Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein; Academic Press Inc Elsevier Science; Experimental Parasitology; 127; 3; 3-2011; 672-679
0014-4894
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.ncbi.nlm.nih.gov/pubmed/21118687
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2010.11.011
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
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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 12.48226

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