Modulation of cardiocyte functional activity by antibodies against trypanosoma cruzi ribosomal P2 protein C terminus.
Antibodies against the Trypanosoma cruzi ribosomal P2beta protein (TcP2beta) have been associated with the chronic cardiac pathology of Chagas' disease in humans. Using synthetic peptides spanning the entire TcP2beta molecule, we investigated their epitope recognition by antibodies from mice chronically infected with T. cruzi and from mice immunized with two recombinant TcP2betas. We found clear differences in epitope recognition between antibodies from T. cruzi-infected mice and mice immunized with two different recombinant TcP2betas associated with different schedules of immunization. Major epitopes recognized by antibodies from mice immunized with recombinant glutathione S-transferase (GST) or histidine (Hist) fusion TcP2beta (GST-TcP2beta or Hist-TcP2beta) are located in the central and hinge regions of the molecule. Nevertheless, mice immunized with Hist-TcP2beta were also able to elicit antibodies against the TcP2beta 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 TcP2beta 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 beta1-adrenergic receptor. Thus, antibodies against the TcP2beta C terminus elicited in the absence of infection are able to modulate a functional activity of host cells through a molecular mimicry mechanism.
Sepulveda
P
P
Laboratoire d'Immunopathogenèse, Département d'Immunologie, Institut Pasteur, 75724 Paris Cedex 15, France.
Liegeard
P
P
Wallukat
G
G
Levin
M J
MJ
Hontebeyrie
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D018604:Epitope Mapping; D006321:Heart / Q000502:physiology*; D007114:Immunization; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D012269:Ribosomal Proteins
D000913:Antibodies, Protozoan; D010750:Phosphoproteins; D018343:Receptors, Adrenergic, beta-2; D012269:Ribosomal Proteins; C031937:phosphoprotein P2, ribosomal