Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein

Valiente-Gabioud, Ariel A; Veaute, Carolina; Perrig, Melina; Galan-Romano, Félix S; Sferco, Silvano J; Marcipar, Iván S (2011). Effect of repetitiveness on the immunogenicity and antigenicity of Trypanosoma cruzi FRA protein. Experimental parasitology, 127(3), pp. 672-9. Amsterdam: Elsevier 10.1016/j.exppara.2010.11.011

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Repetitive proteins (RP) of Trypanosoma cruzi are highly present in the parasite and are strongly recognized by sera from Chagas' disease patients. Flagelar Repetitive Antigen (FRA), which is expressed in all steps of the parasite life cycle, is the RP that displays the greatest number of aminoacids per repeat and has been indicated as one of the most suitable candidate for diagnostic test because of its high performance in immunoassays. Here we analyzed the influence of the number of repeats on the immunogenic and antigenic properties of the antigen. Recombinant proteins containing one, two, and four tandem repeats of FRA (FRA1, FRA2, and FRA4, respectively) were obtained and the immune response induced by an equal amount of repeats was evaluated in a mouse model. The reactivity of specific antibodies present in sera from patients naturally infected with T. cruzi was also assessed against FRA1, FRA2, and FRA4 proteins, and the relative avidity was analyzed. We determined that the number of repeats did not increase the humoral response against the antigen and this result was reproduced when the repeated motifs were alone or fused to a non-repetitive protein. By contrast, the binding affinity of specific human antibodies increases with the number of repeated motifs in FRA antigen. We then concluded that the high ability of FRA to be recognized by specific antibodies from infected individuals is mainly due to a favorable polyvalent interaction between the antigen and the antibodies. In accordance with experimental results, a 3D model was proposed and B epitope in FRA1, FRA2, and FRA4 were predicted.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine

UniBE Contributor:

Perrig, Martin

ISSN:

0014-4894

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:22

Last Modified:

17 Mar 2015 21:00

Publisher DOI:

10.1016/j.exppara.2010.11.011

PubMed ID:

21118687

Web of Science ID:

000288365300008

URI:

https://boris.unibe.ch/id/eprint/7581 (FactScience: 212875)

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