title: Identification of HLA-A∗02:01-restricted CTL epitopes in Trypanosoma cruzi heat shock protein-70 recognized by Chagas disease patients.
abstract: CD8(+) cytotoxic T lymphocyte (CTL) response is critical for controlling the infection of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Since only a few CD8 antigens have been described in Chagas disease patients, the identification of new class I-restricted epitopes is urgently needed for the development of immunotherapies against T. cruzi infection. In this study, bioinformatic methods were used to predict HLA-A∗02:01-binders, and 30 peptides were selected, synthesized and tested for HLA-A∗02:01 binding. Among them, sixteen peptides with medium-to-high affinity were assayed for their recognition by CTL from HSP70-immunized or T. cruzi-infected transgenic B6-A2/K(b) mice. Our results show that four immunodominant epitopes (HSP70(210-8), HSP70(255-63), HSP70(316-24) and HSP70(345-53)) are contained in the T. cruzi HSP70 antigen. Indeed two of them (HSP70(210-8) and HSP70(316-24)) were also recognized by CTL of HLA-A∗02:01(+) Chagas disease patients, indicating that these peptides are processed and displayed as MHC class I epitopes during the natural history of T. cruzi infection. The HLA-A∗02:01 restriction was evidenced using peptide-pulsed K562-A2 cells as antigen-presenting cells. Both cytotoxic and cytokine-secreting activities were detected in response to the former two peptides and, moreover, 10/12 patients (83%) recognized at least one of these two HSP70-derived CD8(+) epitopes.
authors.affiliation: Instituto de Parasitología y Biomedicina López Neyra (CSIC), Parque Tecnológico de Ciencias de la Salud, Avda. del Conocimiento S/N, 18100 Armilla, Spain. concepcion.maranon@genyo.es
authors.forename: Concepción
authors.initials: C
authors.lastname: Marañón
authors.forename: Adriana
authors.initials: A
authors.lastname: Egui
authors.forename: Bartolomé
authors.initials: B
authors.lastname: Carrilero
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Thomas
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Pinazo
authors.forename: Joaquim
authors.initials: J
authors.lastname: Gascón
authors.forename: Manuel
authors.initials: M
authors.lastname: Segovia
authors.forename: Manuel Carlos
authors.initials: MC
authors.lastname: López
mesh_terms: D000328:Adult; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology; D020014:K562 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins; D016056:Immunodominant Epitopes; D010455:Peptides; D015800:Protozoan Proteins