The beta1 adrenergic effects of antibodies against the C-terminal end of the ribosomal P2beta protein of Trypanosoma cruzi associate with a specific pattern of epitope recognition

• Published in: Clinical and experimental immunology 2005-10, Vol.142 (1), p.140-147
• Main Authors: Lopez Bergami, P, Gómez, K A, Levy, G V, Grippo, V, Baldi, A, Levin, M J
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Protozoan - immunology; Autoantibodies - immunology; Autoimmunity - immunology; Chagas Disease - immunology; Chagas Disease - physiopathology; Electrocardiography; Epitope Mapping - methods; Epitopes - immunology; Immunoglobulin G - immunology; Mice; Mice, Inbred BALB C; Protozoan Proteins - immunology; Receptors, Adrenergic, beta-1 - immunology; Recombinant Proteins - immunology; Ribosomal Proteins - immunology; Trypanosoma cruzi - immunology
• ISSN: 0009-9104

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.