A monoclonal antibody against the immunodominant epitope of the ribosomal P2 beta protein of Trypanosoma cruzi interacts with the human beta 1-adrenergic receptor

Monoclonal antibodies were raised against a recombinant ribosomal P2 beta p rotein of Trypanosoma cruzi, One of these reacted with the C terminus of th is protein (peptide R13, EEEDDDMGFGLFD) and epitope mapping confirmed that this epitope was the same as the one defined by the serum of immunized mice , and similar to the previously described chronic Chagas' heart disease (cC hHD) anti-P epitope. Western blotting showed that the monoclonal antibody r ecognized the parasite ribosomal P proteins, as well as the human ribosomal P proteins. Electron microscopy showed that it stained different structure s in parasite and human cells. interestingly, surface plasmon: resonance me asurements indicated that the affinity for the parasite ribosomal P protein epitope (R63) was five times higher than for its human counterpart (peptid e H13, EESDDDMGFGLFD). Since the human epitope contained an acidic region ( EESDDJ similar to the AESDE peptide recognized by cChHD patients in the sec ond extra-cellular loop of the human beta1-adrenergic -adrenergic receptor, the biological activity of the antibody was assessed on neonatal: rat card iomyocytes in culture. The monoclonal antibody had an agonist-like effect. These results, together with the fact that the monoclonal reacted in Wester n blots with the different isoforms of the heart beta1-adrenergic receptor, confirm the possible pathogenic role of antibodies against the parasite ri bosomal P protein based on their cross-reaction with the human beta1-adrene rgic receptor.