Antígenos contendo repetições de aminoácidos como fatores de virulência na infecção pelo Trypanosoma cruzi

Abstract

Using an immunoscreening approach, several antigens derived from a Trypanosoma cruzi amastigote cDNA library that react with sera from chronic chagasic patients were isolated. One such antigen, homologous to the eukaryotic L7a ribosomal protein and containing an Ala-Lys-Pro rich repetitive domain at its N-terminus, was characterized. To evaluate the role of amino acid repeats present in T. cruzi antigens, we generated recombinant versions of the complete antigen (TcL7a) as well as truncated versions containing only its repetitive (TcL7aRep) or the nonrepetitive domain (TcL7aDeltaRep) and used them to immunize mice. Animals immunized with TcL7a produced IgG antibodies against the complete protein as well as against the repetitive domain. On the other hand, mice immunized with TcL7aRep and TcL7aDeltaRep did not generate antibodies against any of these antigens respectively. Regarding cellular immune responses, whereas mice immunized with TcL7a produced high levels of IFN- and IL-10, only very low levels of IFN- were detected in mice immunized with TcL7aRep and TcL7aDeltaRep. After challenging immunized mice with trypomatigotes, we observed a partial protection in mice immunized with the complete protein whereas immunization with TcL7aDeltaRep did not alter parasitemia levels compared to controls. In contrast, immunization with TcL7aRep resulted in an exacerbation of the parasitemia compared to the other groups. Immunization with the repetitive domain followed by immunization with full length L7a protein results in a decreased production of IgG2a against TcL7a and TcL7aRep but does not alter the production of IgG1, IFN- or IL-10. Our results suggest that repetitive domains present in T. cruzi antigens may be used by the parasite to downregulate the Th1 response against the infection