INVESTIGADORES
GOIN Juan Carlos
artículos
Título:
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 receptors without requiring receptor cross-linking.
Autor/es:
CREMASCHI G.; FERNÁNDEZ M.M.; GORELIK G.; GOIN J.C.; FOSSATI C.A.; ZWIRNER N.W.; MALCHIODI E.L.
Revista:
JOURNAL OF NEUROIMMUNOLOGY
Editorial:
Elsevier/North-Holland
Referencias:
Lugar: Amsterdam, Holanda; Año: 2004 vol. 153 p. 99 - 107
ISSN:
0165-5728
Resumen:
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.