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dc.contributor.author
Niborski, Leticia Laura
dc.contributor.author
Potenza, Mariana
dc.contributor.author
Chirivi, Renato G.S.
dc.contributor.author
Simonetti, Leandro
dc.contributor.author
Ossowski, Micaela Soledad
dc.contributor.author
Grippo, Vanina
dc.contributor.author
May, Maria
dc.contributor.author
Staquicini, Daniela I.
dc.contributor.author
Parodi Talice, Adriana
dc.contributor.author
Robello, Carlos
dc.contributor.author
Comini, Marcelo
dc.contributor.author
Alonso, Guillermo Daniel
dc.contributor.author
Raats, Jos M.H.
dc.contributor.author
Gomez, Karina Andrea
dc.date.available
2022-03-17T11:05:07Z
dc.date.issued
2021-01-09
dc.identifier.citation
Niborski, Leticia Laura; Potenza, Mariana; Chirivi, Renato G.S.; Simonetti, Leandro; Ossowski, Micaela Soledad; et al.; Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system.; Elsevier Science; eBioMedicine; 63; 9-1-2021; 1-15
dc.identifier.issn
2352-3964
dc.identifier.uri
http://hdl.handle.net/11336/153501
dc.description.abstract
Background: To deeply understand the role of antibodies in the context of Trypanosoma cruzi infection, we decided to characterize A2R1, a parasite antibody selected from single-chain variable fragment (scFv) phage display libraries constructed from B cells of chronic Chagas heart disease patients. Methods: Immunoblot, ELISA, cytometry, immunofluorescence and immunohistochemical assays were used to characterize A2R1 reactivity. To identify the antibody target, we performed an immunoprecipitation and two-dimensional electrophoresis coupled to mass spectrometry and confirmed A2R1 specific interaction by producing the antigen in different expression systems. Based on these data, we carried out a comparative in silico analysis of the protein target´s orthologues, focusing mainly on post-translational modifications. Findings: A2R1 recognizes a parasite protein of ~50 kDa present in all life cycle stages of T. cruzi, as well as in other members of the kinetoplastid family, showing a defined immunofluorescence labeling pattern consistent with the cytoskeleton. A2R1 binds to tubulin, but this interaction relies on its post-translational modifications. Interestingly, this antibody also targets mammalian tubulin only present in brain, staining in and around cell bodies of the human peripheral and central nervous system. Interpretation: Our findings demonstrate for the first time the existence of a human antibody against T. cruzi tubulin capable of cross-reacting with a human neural protein. This work re-emphasizes the role of molecular mimicry between host and parasitic antigens in the development of pathological manifestations of T. cruzi infection.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
CHAGAS DISEASE
dc.subject
DIGESTIVE SYSTEM
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MOLECULAR MIMICRY
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PHAGE-DISPLAY
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POST-TRANSLATIONAL MODIFICATION
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TUBULIN
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system.
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-12-13T18:56:30Z
dc.journal.volume
63
dc.journal.pagination
1-15
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Niborski, Leticia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Potenza, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Chirivi, Renato G.S.. No especifíca;
dc.description.fil
Fil: Simonetti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Ossowski, Micaela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Grippo, Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: May, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Staquicini, Daniela I.. Universidade Federal de Sao Paulo; Brasil
dc.description.fil
Fil: Parodi Talice, Adriana. Universidad de la República; Uruguay. Instituto Pasteur de Montevideo; Uruguay
dc.description.fil
Fil: Robello, Carlos. Universidad de la República; Uruguay
dc.description.fil
Fil: Comini, Marcelo. Universidad de la Republica; Uruguay
dc.description.fil
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Raats, Jos M.H.. Universidad de la República; Uruguay
dc.description.fil
Fil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.journal.title
eBioMedicine
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S235239642030582X
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ebiom.2020.103206
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