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Identification of major Trypanosoma cruzi antigenic determinants in chronic Chagas' heart disease
M J Levin1, E Mesri, R Benarous
1Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Buenos Aires, Argentina.
Abstract:
To identify Trypanosoma cruzi target antigens in overt Chagas' heart disease, a parasite lambda gt11 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.
Insights
Researchers identified a Trypanosoma cruzi antigen, JL5, predominantly recognized by patients with Chagas' heart disease. This parasite protein shares a similar epitope with human P proteins implicated in systemic lupus erythematosus (SLE).
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Chagas' heart disease is a severe manifestation of Trypanosoma cruzi infection.
- Identifying parasite antigens is crucial for understanding disease pathogenesis and developing diagnostics.
- Cross-reactivity between parasite and host antigens may play a role in autoimmune responses.
Purpose of the Study:
- To identify Trypanosoma cruzi target antigens associated with overt Chagas' heart disease.
- To investigate potential cross-reactivity between Trypanosoma cruzi antigens and host autoimmune targets.
Main Methods:
- Screening of a Trypanosoma cruzi lambda gt11 cDNA library using patient serum.
- Phage dot array immunoassay to probe antigenic clones with sera from infected individuals.
- Nucleotide and amino acid sequencing of identified recombinant antigens.
Main Results:
- A recombinant antigen, JL5, was identified that reacted predominantly with sera from patients with Chagas' heart disease.
- The antigenic determinant of JL5 is a 35 amino acid peptide, identified as the C-terminal portion of a Trypanosoma cruzi P ribosomal protein.
- The JL5 epitope showed high homology to the human P protein epitope, and positive systemic lupus erythematosus (SLE) sera reacted with JL5.
Conclusions:
- The Trypanosoma cruzi P ribosomal protein is a potential target antigen in Chagas' heart disease.
- Antibodies against the Trypanosoma cruzi P protein may share specificity with antibodies found in SLE.
- This cross-reactivity suggests a potential autoimmune component in Chagas' heart disease pathogenesis.