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

JUIZ, NATALIA A.; GIRARD, MAGALI C.; HERNANDEZ, YOLANDA; FRANKE, ANDRE; ACEVEDO, GONZALO R.; PERRI, LUCAS PEREZ; FERNANDEZ, MARISA; WITTIG, MICHAEL; GOMEZ, KARINA A.; ZIBLAT, ANDREA; OSSOWSKI, MICAELA S.; CHADI, RAUL; NIELSEN, MORTEN

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2020 vol. 204 p. 1571 - 1581

0022-1767

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.