The β1 adrenergic effects of antibodies against the C‐terminal end of the ribosomal P2β 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: Bergami, P. Lopez, Gómez, K. A., Levy, G. V., Grippo, V., Baldi, A., Levin, M. J.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Medical sciences; Original; pathogenic antibodies; ribosomal P proteins; Trypanosoma cruzi; β1‐adrenergic receptor
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2005.02885.x

Summary BALB/c mice immunized with recombinant Trypanosoma cruzi ribosomal P2β protein (TcP2β) develop a strong and specific antibody response against its 13 residue‐long C‐terminal epitope (peptide R13: EEEDDDMGFGLFD) that has a concomitant β1‐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 TcP2β. 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 β1‐adrenergic receptor, setting the molecular basis for their pathogenic β1 adrenoceptor stimulating activity.