Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus

Antibodies against the Trypanosoma cruzi ribosomal P2β protein (TcP2β) have been associated with the chronic cardiac pathology of Chagas' disease in humans. Using synthetic peptides spanning the entire TcP2β molecule, we investigated their epitope recognition by antibodies from mice chronically...

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Main Authors: Sepulveda, P., Liegeard, P., Wallukat, G., Levin, M. J., Hontebeyrie, M.
Format: Artigo
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Udgivet: American Society for Microbiology 2000
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Molecular and Cellular Pathogenesis
Online adgang:https://ncbi.nlm.nih.gov/pmc/articles/PMC101752/
https://ncbi.nlm.nih.gov/pubmed/10948133
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spelling pubmed-1017522002-09-12 Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus Sepulveda, P. Liegeard, P. Wallukat, G. Levin, M. J. Hontebeyrie, M. Infect Immun Molecular and Cellular Pathogenesis Antibodies against the Trypanosoma cruzi ribosomal P2β protein (TcP2β) have been associated with the chronic cardiac pathology of Chagas' disease in humans. Using synthetic peptides spanning the entire TcP2β molecule, we investigated their epitope recognition by antibodies from mice chronically infected with T. cruzi and from mice immunized with two recombinant TcP2βs. We found clear differences in epitope recognition between antibodies from T. cruzi-infected mice and mice immunized with two different recombinant TcP2βs associated with different schedules of immunization. Major epitopes recognized by antibodies from mice immunized with recombinant glutathione S-transferase (GST) or histidine (Hist) fusion TcP2β (GST-TcP2β or Hist-TcP2β) are located in the central and hinge regions of the molecule. Nevertheless, mice immunized with Hist-TcP2β were also able to elicit antibodies against the TcP2β C terminus, a region which is highly conserved in both T. cruzi and mammal ribosomal P proteins. Strikingly, antibodies from infected animals recognized only the TcP2β C terminus. By using these antisera with distinct profiles of epitope recognition, it could be shown that only C terminus-specific antibodies were able to increase the beating frequency of cardiomyocytes from neonatal rats in vitro by selective stimulation of the β1-adrenergic receptor. Thus, antibodies against the TcP2β C terminus elicited in the absence of infection are able to modulate a functional activity of host cells through a molecular mimicry mechanism. American Society for Microbiology 2000-09 /pmc/articles/PMC101752/ /pubmed/10948133 Text en Copyright © 2000, American Society for Microbiology
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Molecular and Cellular Pathogenesis
spellingShingle Molecular and Cellular Pathogenesis
Sepulveda, P.
Liegeard, P.
Wallukat, G.
Levin, M. J.
Hontebeyrie, M.
Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus
description Antibodies against the Trypanosoma cruzi ribosomal P2β protein (TcP2β) have been associated with the chronic cardiac pathology of Chagas' disease in humans. Using synthetic peptides spanning the entire TcP2β molecule, we investigated their epitope recognition by antibodies from mice chronically infected with T. cruzi and from mice immunized with two recombinant TcP2βs. We found clear differences in epitope recognition between antibodies from T. cruzi-infected mice and mice immunized with two different recombinant TcP2βs associated with different schedules of immunization. Major epitopes recognized by antibodies from mice immunized with recombinant glutathione S-transferase (GST) or histidine (Hist) fusion TcP2β (GST-TcP2β or Hist-TcP2β) are located in the central and hinge regions of the molecule. Nevertheless, mice immunized with Hist-TcP2β were also able to elicit antibodies against the TcP2β C terminus, a region which is highly conserved in both T. cruzi and mammal ribosomal P proteins. Strikingly, antibodies from infected animals recognized only the TcP2β C terminus. By using these antisera with distinct profiles of epitope recognition, it could be shown that only C terminus-specific antibodies were able to increase the beating frequency of cardiomyocytes from neonatal rats in vitro by selective stimulation of the β1-adrenergic receptor. Thus, antibodies against the TcP2β C terminus elicited in the absence of infection are able to modulate a functional activity of host cells through a molecular mimicry mechanism.
author Sepulveda, P.
Liegeard, P.
Wallukat, G.
Levin, M. J.
Hontebeyrie, M.
author_facet Sepulveda, P.
Liegeard, P.
Wallukat, G.
Levin, M. J.
Hontebeyrie, M.
author_sort Sepulveda, P.
title Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus
title_short Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus
title_full Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus
title_fullStr Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus
title_full_unstemmed Modulation of Cardiocyte Functional Activity by Antibodies against Trypanosoma cruzi Ribosomal P2 Protein C Terminus
title_sort modulation of cardiocyte functional activity by antibodies against trypanosoma cruzi ribosomal p2 protein c terminus
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2000
url https://ncbi.nlm.nih.gov/pmc/articles/PMC101752/
https://ncbi.nlm.nih.gov/pubmed/10948133
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