In silico guided discovery of novel class i and ii trypanosoma cruzi epitopes recognized by T cells from chagas' disease patients

Gonzalo R. Acevedo, Natalia A. Juiz, Andrea Ziblat, Lucas Perez Perri, Magali C. Girard, Micaela S. Ossowski, Marisa Fernandez, Yolanda Hernandez, Raul Chadi, Michael Wittig, Andre Franke, Morten Nielsen, Karina A. Gomez*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

T cell-mediated immune response plays a crucial role in controlling Trypanosoma cruzi infection and parasite burden, but it is also involved in the clinical onset and progression of chronic Chagas' disease. Therefore, the study of T cells is central to the understanding of the immune response against the parasite and its implications for the infected organism. The complexity of the parasite-host interactions hampers the identification and characterization of T cell-activating epitopes. We approached this issue by combining in silico and in vitro methods to interrogate patients' T cells specificity. Fifty T. cruzi peptides predicted to bind a broad range of class I and II HLA molecules were selected for in vitro screening against PBMC samples from a cohort of chronic Chagas' disease patients, using IFN-γ secretion as a readout. Seven of these peptides were shown to activate this type of T cell response, and four out of these contain class I and II epitopes that, to our knowledge, are first described in this study. The remaining three contain sequences that had been previously demonstrated to induce CD8+ T cell response in Chagas' disease patients, or bind HLA-A∗02:01, but are, in this study, demonstrated to engage CD4+ T cells. We also assessed the degree of differentiation of activated T cells and looked into the HLA variants that might restrict the recognition of these peptides in the context of human T. cruzi infection.
Original languageEnglish
JournalJournal of Immunology
Volume204
Issue number6
Pages (from-to)1571-1581
ISSN0022-1767
DOIs
Publication statusPublished - 2020

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