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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.
Blouin et al. (Mon,) studied this question.