CONICET | Buscador de Institutos y Recursos Humanos

Background: Cellular immune response plays a central role in Trypanosoma cruzi infection control, and parasite-specific T cells are found in most chronic Chagas disease patients. The study of their immune repertoire is of key interest for vaccine research. For this purpose, we introduce a bioinformatic predictive approach, which scores the potential immunogenicity of a peptide, and an ulterior validation by ex vivo cellular response evaluation.Methods: Potentially immunogenic peptides were predicted using MHC-Pan and MHC-PanII algorithms from T.cruzi T cell antigens annotated in ImmunoEpitope Database (IEDB), and randomized in 5 pools of 10 peptides each. Their selection was based on high predicted binding to multiple HLA classes I and II alleles prevalent in Latin America. Their capability of inducing cellular response was assessed by Interferon-γ ELISpot on peripheral blood mononuclear cells from chronic patients, in both asymptomatic (n=11) and cardiac (n=9) phases of Chagas disease. Four non-infected individuals were included as controls. Parasite lysate was used as positive control for T.cruzi-specific response.Results: Fifty-four percent of the asymptomatic and 44% of the cardiac patients responded against the lysate. Most subjects responding to peptides pools were asymptomatic, and had also responded to lysate. Cardiac patients exhibited little or no response upon challenge with the peptides. Non-infected individuals did not respond against either parasite lysate or the peptide pools.Conclusions: Bioinformatically predicted peptides succeeded to recall T.cruzi-specific cellular response ex vivo from chronic patients. In particular, 2 out of the 5 randomized peptide pools came out as promising for further evaluation and deconvolution.