Modulatory effects on myocardial physiology induced by an anti-Trypanosoma cruzi monoclonal antibody involve recognition of major antigenic epitopes from b1-adrenergic and M2-muscarinic cholinergic receptors without requiring receptor cross-linking

GRACIELA CREMASCHI,; M FERNÁNDEZ, MARISA; GABRIELA GORELIK,; C GOIN, JUAN; CARLOS ALBERTO FOSSATI; W ZWIRNER, NORBERTO; L MALCHIODI, EMILIO

JOURNAL OF NEUROIMMUNOLOGY

ELSEVIER SCIENCE BV

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 h-adrenergic and muscarinic acetyl choline (mACh) receptors eliciting abnormal physiological responses on normal heart. No crosslinking 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 h1-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 h1- adrenergic and M2-ACh receptors. Its possible relationship with cardiac dysfunction during chronic stage of Chagas? disease is also d. adrenergic and M2-ACh receptors. Its possible relationship with cardiac dysfunction during chronic stage of Chagas? disease is also