In Silico Guided Discovery of Novel Class I and II Trypanosoma cruzi Epitopes Recognized by T Cells from Chagas' Disease Patients.
J Immunol
; 204(6): 1571-1581, 2020 03 15.
Article
en En
| MEDLINE
| ID: mdl-32060134
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*0201, 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
3_ND
Problema de salud:
2_enfermedades_transmissibles
/
3_chagas_disease
/
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Trypanosoma cruzi
/
Linfocitos T CD4-Positivos
/
Cardiomiopatía Chagásica
/
Epítopos de Linfocito T
/
Antígenos de Protozoos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Female
/
Humans
/
Male
País/Región como asunto:
America do sul
/
Argentina
Idioma:
En
Revista:
J Immunol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Argentina