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.
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.
Lopez Bergami
P
P
Laboratorio de Biología Molecular de la Enfermedad de Chagas, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular-Consejo Nacional de Investigaciones Científicas y Técnicas (INGEBI/CONICET), Buenos Aires, Argentina.
Gómez
K A
KA
Levy
G V
GV
Grippo
V
V
Baldi
A
A
Levin
M J
MJ
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000503:physiopathology; D004562:Electrocardiography; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012269:Ribosomal Proteins / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D000913:Antibodies, Protozoan; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D018342:Receptors, Adrenergic, beta-1; D011994:Recombinant Proteins; D012269:Ribosomal Proteins