Key result
Immunization with TcP2beta elicited anti-R13 antibodies in 31 of 50 mice, and recognition of the ExDDxGF motif correlated with the recording of supraventricular tachycardia.
Recognition of the glutamic acid in position 3 of peptide R13 defines the ability of anti-R13 antibodies to react with the beta1-adrenergic receptor, explaining their pathogenic stimulating activity.
Anti-R13 antibodies may stimulate beta1-adrenergic receptors to induce supraventricular tachycardia in this model; leaves open relevance to human Chagas cardiomyopathy.
BALB/c mice immunized with recombinant Trypanosoma cruzi ribosomal P2beta protein (TcP2beta) develop a strong and specific antibody response against its 13 residue-long C-terminal epitope (peptide R13: EEEDDDMGFGLFD) that has a concomitant beta1-adrenergic stimulating activity. However, other animals that undergo similar immunizations seem tolerant to this epitope. To evaluate further the antibody response against the ribosomal P proteins, 25 BALB/c and 25 Swiss mice were immunized with TcP2beta. From the 50 animals, 31 developed a positive anti-R13 response, whereas 19 were non-responsive. From the 31 anti-R13 positive mice, 25 had anti-R13 antibodies that recognized the discontinuous motif ExDDxGF, and their presence correlated with the recording of supraventricular tachycardia. The other six had anti-R13 antibodies but with a normal electrocardiographic recording. These anti-R13 antibodies recognized the motif DDxGF shared by mammals and T. cruzi and proved to be a true anti-P autoantibody because they were similar to those elicited in Swiss, but not in BALB/c mice, by immunization with the C-terminal portion of the mouse ribosomal P protein. Our results show that the recognition of the glutamic acid in position 3 of peptide R13 defines the ability of anti-R13 antibodies to react with the motif AESDE of the second extracellular loop of the beta1-adrenergic receptor, setting the molecular basis for their pathogenic beta1 adrenoceptor stimulating activity.
No takes yet. Share an insight, caveat, or question.
Gómez et al. (2005) studied Trypanosoma cruzi antibody response (n=50). Immunization with recombinant Trypanosoma cruzi ribosomal P2beta protein (TcP2beta) was evaluated on Development of positive anti-R13 response and correlation with supraventricular tachycardia. Immunization with TcP2beta elicited anti-R13 antibodies in 31 of 50 mice, and recognition of the ExDDxGF motif correlated with the recording of supraventricular tachycardia.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: