title: Differential phenotypic and functional profiles of TcCA-2 -specific cytotoxic CD8+ T cells in the asymptomatic versus cardiac phase in Chagasic patients.
abstract: It has been reported that the immune response mediated by T CD8+ lymphocytes plays a critical role in the control of Trypanosoma cruzi infection and that the clinical symptoms of Chagas disease appear to be related to the competence of the CD8+ T immune response against the parasite. Herewith, in silico prediction and binding assays on TAP-deficient T2 cells were used to identify potential HLA-A*02:01 ligands in the T. cruzi TcCA-2 protein. The TcCA-2-specific CD8+ T cells were functionality evaluated by Granzyme B and cytokine production in peripheral blood mononuclear cells (PBMC) from Chagas disease patients stimulated with the identified HLA-A*02:01 peptides. The specific cells were phenotypically characterized by flow cytometry using several surface markers and HLA-A*02:01 APC-labeled dextramer loaded with the peptides. In the T. cruzi TcCA-2 protein four T CD8+ epitopes were identified which are processed and presented during Chagas disease. Interestingly, a differential cellular phenotypic profile could be correlated with the severity of the disease. The TcCA-2-specific T CD8+ cells from patients with cardiac symptoms are mainly effector memory cells (TEM and TEMRA) while, those present in the asymptomatic phase are predominantly naive cells (TNAIVE). Moreover, in patients with cardiac symptoms the percentage of cells with senescence features is significantly higher than in patients at the asymptomatic phase of the disease. We consider that the identification of these new class I-restricted epitopes are helpful for designing biomarkers of sickness pathology as well as the development of immunotherapies against T. cruzi infection.
authors: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS Granada, Avda. del Conocimiento S/N, 18016, Granada, Spain.
authors: Adriana
authors: A
authors: Egui
authors: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS Granada, Avda. del Conocimiento S/N, 18016, Granada, Spain.
authors: M Carmen
authors: MC
authors: Thomas
authors: Unidad Regional de Medicina Tropical, Hospital Virgen de la Arrixaca, Carretera Madrid-Cartagena s/n, El Palmar, 30120, Murcia, Spain.
authors: Bartolomé
authors: B
authors: Carrilero
authors: Unidad Regional de Medicina Tropical, Hospital Virgen de la Arrixaca, Carretera Madrid-Cartagena s/n, El Palmar, 30120, Murcia, Spain.
authors: Manuel
authors: M
authors: Segovia
authors: Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
authors: Carlos
authors: C
authors: Alonso
authors: Genomic Medicine Department, Centre for Genomics and Oncological Research (GENYO): Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Spain.
authors: Concepción
authors: C
authors: Marañón
authors: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), PTS Granada, Avda. del Conocimiento S/N, 18016, Granada, Spain.
authors: Manuel Carlos
authors: MC
authors: López
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002460:Cell Line; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D000939:Epitopes; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D010641:Phenotype
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens