Infection and Immunity, September 2000, p. 5114-5119, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Laboratoire d'Immunopathogenèse, Département d'Immunologie, Institut Pasteur, 75724 Paris Cedex 15, France1; Department of Cardiology, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany2; and INGEBI, 1428 Buenos Aires, Argentina3
Received 14 February 2000/Returned for modification 5 April 2000/Accepted 23 June 2000
Antibodies against the Trypanosoma cruzi ribosomal
P2
protein (TcP2
) have been associated with the chronic cardiac
pathology of Chagas' disease in humans. Using synthetic peptides
spanning the entire TcP2
molecule, we investigated their epitope
recognition by antibodies from mice chronically infected with T. cruzi and from mice immunized with two recombinant TcP2
s. We
found clear differences in epitope recognition between
antibodies from T. cruzi-infected mice and mice immunized
with two different recombinant TcP2
s associated with
different schedules of immunization. Major epitopes recognized by
antibodies from mice immunized with recombinant glutathione
S-transferase (GST) or histidine (Hist) fusion TcP2
(GST-TcP2
or Hist-TcP2
) are located in the central
and hinge regions of the molecule. Nevertheless, mice immunized with
Hist-TcP2
were also able to elicit antibodies against the TcP2
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 TcP2
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
1-adrenergic receptor. Thus,
antibodies against the TcP2
C terminus elicited in the absence of
infection are able to modulate a functional activity of host cells
through a molecular mimicry mechanism.
Present address: C/Olivereta 40, 46018 Valencia, Spain.
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