Trypanosoma cruzi: Immune Response and Functional Heart Damage Induced in Mice by the Main Linear B-Cell Epitope of Parasite Ribosomal P Proteins

Abstract

Motrán, C. C., Cerbán, F. M., Rivarola, W., Iosa, D., and Vottero de Cima, E. 1998.Trypanosoma cruzi: Immune response and functional heart damage induced in mice by the main linear B-cell epitope of parasite ribosomal P proteins.Experimental Parasitology88, 223–230. We report herein on the specific and autoimmune humoral response generated by the immunization of mice with the R13 synthetic peptide coupled to a carrier protein, OVA. This peptide correspons to the C-terminal region ofTrypanosoma cruziribosomal P1 and P2 proteins (EEEDDDMGFGLFD), a sequence that differs from the other eukariotic P consensus sequence (EESDDDMGFGLFD) only in a nonconservative amino acid substitution. The antibody response studied by ELISA revealed that all R13-immunized mice had antibodies against R13, consisting mainly of IgG1 and IgG2 isotypes, even though IgG3 and IgE isotypes were also observed. The self-reactivity of anti-R13 sera assayed by immunoblot, revealed that all sera contained IgG antibodies binding to mouse and human 38-kDa heart antigen. This antigenic band binds several immunoglobulin isotypes (IgG2 > IgG3 > IgE > IgG1). The specificity of anti-R13 antibodies analyzed by competitive inhibition of R13 ELISA using R13 and R7 (MGFGLFD) peptides revealed that the reactivity of the induced anti-P antibodies was not absorbed by R7. Therefore, the main immunogenic region of R13 for mouse would be EEEDDD, which contains the amino acid substitution. In parallel with this humoral response, both partial protection and heart damage were observed in R13-immunized mice. In fact, the R13-immunized mice showed significantly lower parasitemia and longer survival than the control animals. In addition, all R13-immunized mice showed electrocardiographic changes (bradycardia, prolonged PQ segment, and intraventricular conduction disturbances), which are typical findings in Chagas disease patients. This study represents the first definitive report in which one defined B-cell epitope, the single peptide R13 fromT. cruzi, coupled to a carrier protein was able to induce specific and autoreactive antibodies as well as to generate heart functional alterations.