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Recombinant antibod...
Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system
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- Niborski, Leticia L. (author)
- Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina.;PSL Res Univ, Inst Curie, Translmm Team, INSEAM U932, Paris, France.
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- Potenza, Mariana (author)
- Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina.
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- Chirivi, Renato G. S. (author)
- ModiQuest BV, Oss, Netherlands.
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- Simonetti, Leandro (author)
- Uppsala universitet,Biokemi
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- Ossowski, Micaela S. (author)
- Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina.
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- Grippo, Vanina (author)
- Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina.;Consejo Nacl Invest Cient & Tecn, ICT Milstein, Ctr Virol Anim CEVAN, Buenos Aires, DF, Argentina.
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- May, Maria (author)
- Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt IBYME, Buenos Aires, DF, Argentina.
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- Staquicini, Daniela, I (author)
- Univ Fed Sao Paulo, Dept Microbiol Inmunol & Parasitol, Escola Paulista Med, Sao Paulo, SP, Brazil.;Rutgers Canc Inst New Jersey, Newark, NJ USA.;Rutgers New Jersey Med Sch, Dept Radiat Oncol, Div Canc Biol, Newark, NJ USA.
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- Parodi-Talice, Adriana (author)
- Inst Pasteur Montevideo, Unidad Biol Mol, Montevideo, Uruguay.;Univ Republica, Fac Ciencias, Secc Genet, Montevideo, Uruguay.
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- Robello, Carlos (author)
- Inst Pasteur Montevideo, Unidad Biol Mol, Montevideo, Uruguay.;Univ Republica, Fac Med, Dept Bioquim, Montevideo, Uruguay.
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- Comini, Marcelo A. (author)
- Inst Pasteur Montevideo, Grp Redox Biol Trypanosomes, Montevideo, Uruguay.
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- Alonso, Guillermo D. (author)
- Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina.
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- Raats, Jos M. H. (author)
- ModiQuest BV, Oss, Netherlands.
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- Gomez, Karina A. (author)
- Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina.
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Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina;PSL Res Univ, Inst Curie, Translmm Team, INSEAM U932, Paris, France. Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol INGEBI, Buenos Aires, DF, Argentina. (creator_code:org_t)
- Elsevier, 2021
- 2021
- English.
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 63
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Abstract
Subject headings
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- 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 targets orthologues, focusing mainly on post-translational modifications. Findings: A2R1 recognizes a parasite protein of similar to 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Chagas disease
- Phage-display
- Tubulin
- Molecular mimicry
- Post-translational modification
- Digestive system
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Niborski, Letici ...
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Potenza, Mariana
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Chirivi, Renato ...
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Simonetti, Leand ...
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Ossowski, Micael ...
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Grippo, Vanina
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May, Maria
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Staquicini, Dani ...
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Parodi-Talice, A ...
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Robello, Carlos
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Comini, Marcelo ...
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Alonso, Guillerm ...
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Raats, Jos M. H.
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Gomez, Karina A.
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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EBioMedicine
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Uppsala University