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| Item Type: | Article |
|---|---|
| Title: | Molecular mimicry between the immunodominant ribosomal protein PO of Trypanosoma cruzi and a functional epitope on the human beta1-adrenergic receptor |
| Creators Name: | Ferrari, I. and Levin, M.J. and Wallukat, G. and Elies, R. and Lebesgue, D. and Chiale, P. and Elizari, M. and Rosenbaum, M. and Hoebeke, J. |
| Abstract: | 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. |
| Keywords: | Amino Acid Sequence, Amino Acid Sequence Homology, Autoantibodies, Autoantigens, Autoimmune Diseases, beta-1 Adrenergic Receptors, Bisoprolol, Chagas Cardiomyopathy, Chagas Disease, Cross Reactions, Cultured Cells, Immunodominant Epitopes, Leishmania Donovani, Leishmaniasis, Molecular Mimicry, Molecular Sequence Data, Myocardial Contraction, Myocardium, Phosphoproteins, Protozoan Antibodies, Protozoan Antigens, Recombinant Proteins, Ribosomal Proteins, Sequence Alignment, Trypanosoma Cruzi, Visceral Leishmaniasis, Animals, Rats |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 182 |
| Number: | 1 |
| Page Range: | 59-65 |
| Date: | 1 July 1995 |
| Official Publication: | https://doi.org/10.1084/jem.182.1.59 |
| PubMed: | View item in PubMed |
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