Our studies are aimed to understand the role of molecular mimicry between the molecules of Trypanosoma cruzi (agent of Chagas disease) and of the host (man) in the cardiac pathology of Chagas disease. Anti-ribosomal P2 acidic protein response was studied because it is associated to chronic Chagas heart disease. A monoclonal antibody was defined by its specificity against the well conserved C terminus of the molecule and by its chronotropic effect on cardiocytes in vitro. Its activity in vivo is currently studied.

Screening of a cDNA library from Trypanosoma cruzi with sera from chronic Chagas heart disease patients allows the identification of a parasite polypeptide specifically recognized by sera from patients with cardiomyopathy. This polypeptide is part of a ribosomal P2 protein (Tc-P2) of acidic ribosomal protein' family. A unique epitope is recognized that is located at the C terminus of the molecule whose sequence is very conserved. Particularly, the sequence of its human counterpart differs only in aminoacid at position 11, where a serine is replacing a glutamic acid. A monoclonal antibody specific of Tc-P2 C terminus (mAb 17.2) recognizes an epitope on the second extra-cellular loop of the b1-adrenergic receptor on cardiocytes in vitro. It exerts a chronotropic effect and its activity is currently studied in vivo.
Attempts for crystallization of the mAb 17.2-Fab with Tc-P2 have been started. The definition of the interactions of the antibody with specific aminoacids of the b1-adrenergic receptor might contribute to the design of new beta-blocking drugs useful for patients with Chagas disease but also for patients with idiopathic dilated cardiomyopathy that has some common features and whose etiology is still unknown.

HONTEBEYRIE Mireille, Chef de laboratoire Institut Pasteur

GREGOIRE Josiane, Technicienne supérieure Institut Pasteur