Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.
Article|
July 01 1995
Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.
I Ferrari,
I Ferrari
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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M J Levin,
M J Levin
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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G Wallukat,
G Wallukat
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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R Elies,
R Elies
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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D Lebesgue,
D Lebesgue
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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P Chiale,
P Chiale
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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M Elizari,
M Elizari
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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M Rosenbaum,
M Rosenbaum
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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J Hoebeke
J Hoebeke
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
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I Ferrari
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
M J Levin
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
G Wallukat
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
R Elies
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
D Lebesgue
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
P Chiale
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
M Elizari
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
M Rosenbaum
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
J Hoebeke
Laboratorio de Biologia Molecular de la Enfermedad de Chagas, INGEBI (CONICET), Buenos Aires, Argentina.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 182 (1): 59–65.
Citation
I Ferrari, M J Levin, G Wallukat, R Elies, D Lebesgue, P Chiale, M Elizari, M Rosenbaum, J Hoebeke; Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.. J Exp Med 1 July 1995; 182 (1): 59–65. doi: https://doi.org/10.1084/jem.182.1.59
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