TY - JOUR
T1 - 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
AU - Egui, Adriana
AU - Thomas, M. Carmen
AU - Morell, María
AU - Marañón, Concepción
AU - Carrilero, Bartolomé
AU - Segovia, Manuel
AU - Puerta, Concepción J.
AU - Pinazo, María Jesús
AU - Rosas, Fernando
AU - Gascón, Joaquim
AU - López, Manuel Carlos
N1 - Funding Information:
We are grateful to Prof. M.E. Patarroyo for his help in the peptide synthesis. We thank A. Lopez-Barajas (IPBLN-CSIC) for her technical assistance in the purification of the recombinant proteins and purification of PFRs specific antibodies; A.I. Fernandez and L. Montosa (IPBLN-CSIC) for their technical assistance in the purification of peripheral mononuclear cells from blood samples; B. Rojas (IPBLN-CSIC) for her technical assistance in the indirect immunofluorescence assays. Dr. M.A. López-Nevot and A. Moreno, Hospital Universitario Virgen de las Nieves, for HLA-A typing and Dr. C. Britten (Johanes Gutenberg-University) for the K562-A2 cell line. We also thank to Dr. L. Murcia and A. Iborra from Hospital Virgen de la Arrixaca (Murcia, Spain) for collecting human biological samples. This work was supported by grants P08-CVI-04037PAI ( Junta de Andalucía ), BFU2010-1670 from Plan Nacional I+D+i (MICINN) , RD06/0021/0014 and RD06/0021/1007 – ISCIII-RETIC (MICINN, Spain) and FEDER . MS and BC were supported by grant FIS, 2009SGR385 from ISCIII (MICINN, Spain) .
PY - 2012/10
Y1 - 2012/10
N2 - 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/Kb transgenic mice with plasmids coding for the fusion proteins PFR2-HSP70 and PFR3-HSP70 induced a specific CTL response against two PFRs epitopes (PFR2449-457 and PFR3481-489), and showed specific lysis percentages of 24 and 12, respectively. Moreover, the PFR219-28, PFR2156-163, PFR2449-457, PFR3428-436, PFR3475-482 and PFR3481-489 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 PFR2156-163 and PFR2449-457 peptides, two out of 11 patients in response to PFR219-28 peptide and one out of 14 and 11 patients in response to PFR3428-436 and PFR3481-489 peptides, respectively. The PFRs-specific cytotoxic activity in purified PBMC was only detected in patients in the indeterminate phase of the disease.
AB - 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/Kb transgenic mice with plasmids coding for the fusion proteins PFR2-HSP70 and PFR3-HSP70 induced a specific CTL response against two PFRs epitopes (PFR2449-457 and PFR3481-489), and showed specific lysis percentages of 24 and 12, respectively. Moreover, the PFR219-28, PFR2156-163, PFR2449-457, PFR3428-436, PFR3475-482 and PFR3481-489 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 PFR2156-163 and PFR2449-457 peptides, two out of 11 patients in response to PFR219-28 peptide and one out of 14 and 11 patients in response to PFR3428-436 and PFR3481-489 peptides, respectively. The PFRs-specific cytotoxic activity in purified PBMC was only detected in patients in the indeterminate phase of the disease.
KW - CD8 T epitope
KW - Chagas disease
KW - Cytotoxic T lymphocytes
KW - Paraflagellar rod proteins (PFRs)
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=84863003591&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2012.05.021
DO - 10.1016/j.molimm.2012.05.021
M3 - Article
C2 - 22750229
AN - SCOPUS:84863003591
SN - 0161-5890
VL - 52
SP - 289
EP - 298
JO - Molecular Immunology
JF - Molecular Immunology
IS - 3-4
ER -
