A functional network of intramolecular cross-reacting epitopes delays the elicitation of neutralizing antibodies to Trypanosoma cruzi trans-sialidase.
Trypanosoma cruzi trans-sialidase (TS) constitutes a key molecule in both the establishment of the infection and in the development of pathologic abnormalities associated with Chagas disease. Several cross-reactive epitopes located in its catalytic region were previously identified. In the present study, a panel of enzymes altered in these epitopes were generated to analyze their in vivo significance. Although displaying similar specific activity, thermal stability, and overall antigenic structure, mutant TS proteins elicited an improved neutralizing response, compared with that in the parent, wild-type molecule. These features support an in vivo role for cross-reactive epitopes in dampening the elicitation of TS-neutralizing antibodies. Structural and immunological evidence indicating that the epitope cross-reactivity could be extended to the highly immunogenic SAPA repeats located on the TS C terminus is also reported. This complex cross-reactive epitope cargo might represent a novel strategy, providing secreted virulence factors with the ability to delay an effective elicitation of humoral response.
Pitcovsky
Tamara A
TA
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín, Buenos Aires, Argentina. tamarap@iib.unsam.edu.ar
Buscaglia
Carlos A
CA
Mucci
Juan
J
Campetella
Oscar
O
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D006023:Glycoproteins; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009439:Neuraminidase / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
D000913:Antibodies, Protozoan; D016054:DNA, Protozoan; D000939:Epitopes; D006023:Glycoproteins; D011994:Recombinant Proteins; C069715:trans-sialidase; D009439:Neuraminidase