Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma crnzi and a functional epitope on the humanβ1-adrenergic receptor

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 β1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human β1-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-β (AESEE). Concomitantly, recognition of P0-β was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-β, and H26R, but not by a peptide corresponding to the second extracellular loop of the human β2-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 β1 blocker bisoprolol and the peptide P0-β. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human β1-adrenergic receptor through a molecular mimicry mechanism. © 1995, Rockefeller University Press., All rights reserved.