Modulatory effects on myocardial physiology induced by an anti-Trypanosoma cruzi monoclonal antibody involve recognition of major antigenic epitopes from beta1-adrenergic and M2-muscarinic cholinergic recpetors without requiring receptor cross-linking

CREMASCHI G; FERNÁNDEZ MM; GOERLIK G; GOIN J,; FOSSATI CA; ,ZWIRNER NW; MALCHIODI E.L

JOURNAL OF NEUROIMMUNOLOGY

ELSEVIER

Lugar: New York; Año: 2004 vol. 153 p. 99 - 107

0165-5728

It has been proposed that anti-myocardial antibodies (Ab) against neurotransmitter (NT) receptors are involved in the immunopathology of chronic Chagas´ heart disease. We demonstrated that an anti-Trypanosoma cruzi monoclonal Ab (mAb), CAK20.12, binds to murine cardiac beta-adrenergic and muscarinic acetyl choline (mACh) receptors eliciting abnormal physiological responses on normal heart. No cross-linking requirement for mAb actions was demonstrated using Fab fragment derived from CAK20.12. mAb binding to synthetic peptides from the second extracellular loop of both beta1-adrenergic and mACh receptors, demonstrated by ELISA, identified the region of NT receptors involved. Cross-reactivity between these peptides and T. cruzi antigen was confirmed by binding inhibition assays. These results support the existence of cross-reactivity due to molecular mimicry between a parasite antigen and the major antigenic epitopes present on both beta1-adrenergic and M2-ACh receptors. Its possible relationship with cardiac dysfunction during chronic stage of Chagas´ disease is also discussed.