In Silico guided discovery of Novel Class I and II Trypanosoma cruzi Epitopes recognized by T Cells from Chagas' disease patients

Fil: Acevedo, Gonzalo R. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr. Héctor N. Torres; Argentina.Fil: Juiz, Natalia A. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr. Héctor N. Torres; Argentina.Fil: Ziblat, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental; Argentina.Fil: Pérez Perri, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr. Héctor N. Torres; Argentina.Fil: Girard, Magalí C. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr. Héctor N. Torres; Argentina.Fil: Ossowski, Micaela S. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr. Héctor N. Torres; Argentina.Fil: Fernández, Marisa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Hernández, Yolanda. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Chadi, Raúl. Hospital General de Agudos Dr. Ignacio Pirovano; Argentina.Fil: Wittig, Michael. Christian-Albrechts-University of Kiel. Institute of Clinical Molecular Biology; Alemania.Fil: Franke, Andre. Christian-Albrechts-University of Kiel. Institute of Clinical Molecular Biology; Alemania.Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Gómez, Karina A. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr. Héctor N. Torres; Argentina.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