MOLECULAR MIMICRY BETWEEN THE IMMUNODOMINANT RIBOSOMAL-PROTEIN PO OF TRYPANOSOMA-CRUZI AND A FUNCTIONAL EPITOPE ON THE HUMAN BETA(1)-ADRENERGIC RECEPTOR

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal PO 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 PO 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 PO-14i (AAAESEEEDDDDDF) and PO-beta (AESEE). Concomitantly, recognition of PO-beta was inhibited with the H26R peptide. Recognition of PO in Western blots was inhibited by PO-14i, PO-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 PO-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.