Immunization with the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins induces long-term duration cross-reactive antibodies with heart functional and structural alterations in young and aged mice

The R13 peptide sequence (EEEDDDMGFGLFD) that corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins differs from the eukariotic P concensus sequence EESDDDMGFGLFD (H13) only in a nonconservati ve amino acid substitution. The immunization of BALB/c mice with R13 synthe tic peptide coupled to a carrier protein (OVA) induces specific (anti-R13) and autoreactive (anti-H13 and anti-heart) antibodies as well as heart func tional alterations. Since aged human and experimental animals are impaired in their responses to most foreign antigens but they produce greater amount s of autoantibodies, in this work we used aged mice as an experimental mode l able to exaggerate the autoimmune component of the R13-induced response i n case it was present. We studied whether these antibodies generated in the absence of the parasite would induce pathological changes in heart tissues , The levels of antibodies against R13 (foreign antigen) and H13 (autoantig en) studied comparatively in 2- and 12-month-old mice 10 days after the thi rd immunization with R13 coupled to OVA were, as me expected for a foreign antigen, higher in almost all sera from a-month-old mice tested than in ser a from 12-month-old mice. Besides, these specific and cross-reactive antibo dy response remain elevated as long as 150 days post third immunization. In addition, the isotype pattern that recognizes R13 and the self-sequence H1 3 showed no differences between sera from young and aged mice. Moreover, wh en ECG traces were obtained from immunized mice, the heart functional alter ations observed at 10 days continued at 80 and 150 days after the third imm unization, showing an association with the levels of antibodies. In additio n, despite the fact that the heart tissue morphology showed no alterations 10 days post third immunization, several abnormalities in the tissue archit ecture were revealed at 80 and 150 days post third immunization, This repor t demonstrates the biological relevance of R13-induced cross-reactive antib odies in some of the electrophysiologic and histological changes found in T . cruzi-infected mammalians. (C) 2000 Academic Press.