In Silico Guided Discovery of Novel Class I and II Trypanosoma cruzi Epitopes Recognized by T Cells from Chagas' Disease Patients.

Authors:
Gonzalo R Acevedo, Natalia A Juiz, Andrea Ziblat, Lucas Pérez Perri, Magalí C Girard, Micaela S Ossowski, Marisa Fernández, Yolanda Hernández, Raúl Chadi, Michael Wittig, Andre Franke, Morten Nielsen, Karina A Gómez
Year of publication:
2020
Volume:
-
Issue:
-
Issn:
0022-1767
Journal title abbreviated:
J IMMUNOL
Journal title long:
The journal of immunology
Impact factor:
4.886
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.