title: Trypanosoma cruzi paraflagellar rod proteins 2 and 3 contain immunodominant CD8(+) T-cell epitopes that are recognized by cytotoxic T cells from Chagas disease patients.
abstract: The protozoan parasite Trypanosoma cruzi is the etiological agent of Chagas disease. To date, no vaccine is available for protection against T. cruzi infection. The CD8(+) T cells immune response against specific antigens has shown to efficiently control the spread of the parasite in murine experimental infection. However, data concerning CD8(+) response in Chagas patients are still restricted to a few epitopes. We have studied the existence of immunodominant CD8(+) T cell epitopes in the paraflagellar rod proteins 2 and 3 (PFR2 and PFR3) from T. cruzi in a mouse model, and analyzed their recognition by cytotoxic T lymphocytes from Chagas disease patients. Immunization of C57BL/6-A2/K(b) transgenic mice with plasmids coding for the fusion proteins PFR2-HSP70 and PFR3-HSP70 induced a specific CTL response against two PFRs epitopes (PFR2(449-457) and PFR3(481-489)), and showed specific lysis percentages of 24 and 12, respectively. Moreover, the PFR2(19-28), PFR2(156-163), PFR2(449-457), PFR3(428-436), PFR3(475-482) and PFR3(481-489) peptides were observed to have a high binding affinity to the HLA-A*02:01 molecule. Remarkably, these HLA-A*02:01-binding peptides are successfully processed and presented during natural infection by T. cruzi in the context of MHC class I as evidenced by using peptide-pulsed K562-A2 cells as antigen presenting cells. The T cells from Chagas disease chronic patients specific for PFR2/PFR3 selected CD8(+) epitopes showed a pro-inflammatory cytokine secretion profile (IFN-γ, TNF-α and IL-6). A positive Granzime B secretion was observed in three out of 16 patients in response to PFR2(156-163) and PFR2(449-457) peptides, two out of 11 patients in response to PFR2(19-28) peptide and one out of 14 and 11 patients in response to PFR3(428-436) and PFR3(481-489) peptides, respectively. The PFRs-specific cytotoxic activity in purified PBMC was only detected in patients in the indeterminate phase of the disease.
authors: Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento S/N, 18100-Granada, Spain.
authors: Adriana
authors: A
authors: Egui
authors: M Carmen
authors: MC
authors: Thomas
authors: María
authors: M
authors: Morell
authors: Concepción
authors: C
authors: Marañón
authors: Bartolomé
authors: B
authors: Carrilero
authors: Manuel
authors: M
authors: Segovia
authors: Concepción J
authors: CJ
authors: Puerta
authors: María Jesús
authors: MJ
authors: Pinazo
authors: Fernando
authors: F
authors: Rosas
authors: Joaquim
authors: J
authors: Gascón
authors: Manuel Carlos
authors: MC
authors: López
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015800:Protozoan Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins; D016056:Immunodominant Epitopes; D015850:Interleukin-6; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C045519:paraflagellar rod proteins, Trypanosoma brucei; D007371:Interferon-gamma; D053804:Granzymes