Identification of Major Trypanosoma Cruzi Antigenic Determinants in Chronic Chagas' Heart Disease

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  • Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Unité 15 INSERM, Servicio de Cardiología, Hospital Ramos Mejía, Instituto Nacional de Diagnóstico e Investigación de la Enfermedad de Chagas “Mario Fatala Chabén,”, Unité 129 INSERM, Buenos Aires, Argentina

To identify Trypanosoma cruzi target antigens in overt Chagas' heart disease, a parasite λgt11 cDNA library was screened with the serum of a patient with a severe chagasic heart involvement (JL). Using a phage dot array immunoassay, 5 highly antigenic clones, JL1, JL5, JL7, JL8, and JL9, were probed with sera from clinically characterized T. cruzi infected subjects. The correlation of cloned T. cruzi antigen recognition with the clinical status of the subjects led to the identification of a recombinant antigen, JL5, that reacted predominantly with sera from patients with Chagas' heart disease. The antigenic determinant of the JL5 recombinant was a small 35 amino acid peptide. The nucleotide and the deduced amino acid sequence, together with other experimental data, allowed identification as the C-terminal portion of a T. cruzi P ribosomal protein. The C-terminal undecapeptide in JL5, EDDDMGFGLFD, was highly homologous to the same region of the human P protein SD(D/E)DMGFGLFD. The latter sequence has been identified as the P protein epitope in systemic lupus erythematosus (SLE). Positive SLE sera reacted with the JL5 recombinant phage, suggesting that the T. cruzi P protein might induce antibodies with a similar specificity to that of P antibodies in SLE.