Modulation of cardiocyte functional activity by antibodies against Trypanosoma cruzi ribosomal P2 protein C terminus

Antibodies against the Trpanosoma cruzi ribosomal P2 beta protein (TcP2 bet a) have been associated with the chronic cardiac pathology of Chagas' disea se in humans. Using synthetic peptides spanning the entire TcP2 beta molecu le, we investigated their epitope recognition by antibodies from mice chron ically infected with T. cruzi and from mice immunized with two recombinant TcP2 beta s. We found clear differences in epitope recognition between anti bodies from T. cruzi-infected mice and mice immunized with two different re combinant TcP2 beta s associated with different schedules of immunization. Major epitopes recognized by antibodies from mice immunized with recombinan t glutathione S-transferase (GST) or histidine (Hist) fusion TcP2 beta (GST -TcP2 beta or Hist-TcP2 beta) are located in the central and hinge regions of the molecule. Nevertheless, mice immunized with Hist-TcP2 beta mere also able to elicit antibodies against the TcP2 beta C terminus, a region which is highly conserved in both T. cruzi and mammal ribosomal P proteins. Stri kingly, antibodies from infected animals recognized only the TcP2 beta C te rminus. By using these antisera with distinct profiles of epitope recogniti on, it could be shown that only C terminus-specific antibodies mere able to increase the beating frequency of cardiomyocytes from neonatal rats in vit ro by selective stimulation of the beta 1-adrenergic receptor. Thus, antibo dies against the TcP2 beta C terminus elicited in the absence of infection are able to modulate a functional activity of host cells through a molecula r mimicry mechanism.