Major Trypanosoma cruzi antigenic determinant in Chagas' heart disease shares homology with the systemic lupus erythematosus ribosomal P protein epitope

Abstract

A Trypanosoma cruzi Xgtll cDNA clone, JL5, expressed a recombinant protein which was found to react predominantly with chronic Chagas' heart disease sera. The cloned 35-residue-long peptide was identified as the carboxyl-terminal portion of a T. cruzi ribosomal P protein. The JL5 13 carboxyl-terminal residues shared a high degree of homology with the systemic lupus erythematosus (SLE) ribosomal P protein epitope. Synthetic peptides comprising the 13 (R-13), 10 (R-10), and 7 (R-7) carboxyl-terminal residues of the JL5 protein were used to study, by enzyme-linked immunosorbent assay, the specificity of the Chagas' disease anti-JL5 and SLE

Humoral autoimmune response in Chagas' disease: Trypanosoma cruzi ribosomal antigens as immunizing agents

“…It has been proposed that all T. cruzi P proteins are able to generate autoimmune responses [16,17,19,32], although until now only the autoreactive nature of immunopurified antibodies against the C-terminal region of the T. cruzi low molecular weight P proteins has been established [17]. For this reason we will restrict our analysis to this antibody response.…”

“…The main linear epitope(s) of the T. cruzi P1 and P2 type proteins have been mapped to the 13 C-terminal amino acid sequence (R-13) EEED-DDMGFGLFD, which is almost identical to the eukaryotic P consensus sequence, except for the non-conservative amino acid substitution of the Ser by a Glu residue ( Table 2) [16][17][18]. This change generates a more hydrophilic sequence, EEEDDD, which is critical in determining the immunological reactivity of the T. cruzi R-13 epitope in Chagas' disease [16]. The anti-R13 response correlates significantly with the anti-T. cruzi response of chagasic sera [17].…”

“…Since the intracellu- Table 1 T. cruzi antigens that induce autoreactive antibodies T. cruzi Synonym Immunopurified antibodies antigens to the parasite antigens bind to: TcP2a [27] TcP2b [14] Hs P1 and P2 [16,17] TcP2/3 [27] TcPJL5 [12] Hs P1 and P2 [16,17] TcP1 [13] Hs P1 and P2 [16,17] F1 160 [15] 48 kDa intracellular axonal protein [15] Legend Table 1: Hs, Homo sapiens lar forms of the parasite are rarely found in chagasic myocarditis,'the hypothesis of an autoimmune process has been proposed [1][2][3][4][5].…”

“…The anti-Fl-160 antibodies recognize a 48 kDa intracellular axonal protein of yet unknown amino acid sequence [15]. The antibodies that react with the low molecular weight T. cruzi ribosomal P proteins recognize the human counterparts of these proteins, the ribosomal P1 and P2 proteins, which are also targets of the auto anti-P-antibodies in systemic lupus erythematosus (SLE) [16][17][18]. Interestingly, antibodies to T. cruzi ribosomal P proteins in Chagas' disease and anti-P antibodies in SLE share the same specificity, since they recognize the 13 C-terminal residues of parasite and host P proteins [16,17,19].…”

“…The antibodies that react with the low molecular weight T. cruzi ribosomal P proteins recognize the human counterparts of these proteins, the ribosomal P1 and P2 proteins, which are also targets of the auto anti-P-antibodies in systemic lupus erythematosus (SLE) [16][17][18]. Interestingly, antibodies to T. cruzi ribosomal P proteins in Chagas' disease and anti-P antibodies in SLE share the same specificity, since they recognize the 13 C-terminal residues of parasite and host P proteins [16,17,19]. This fact makes it possible to compare the fine specificity of the auto anti-ribosomal P protein response in SLE and Chagas' disease, an analysis that may be of importance for the understanding of the immunopathology of the disease.…”