Identification of HLA-A*02:01-restricted CTL epitopes in Trypanosoma cruzi heat shock protein-70 recognized by Chagas disease patients

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 (H5P70(210-8), H5P70(255-63). HSP70(316-24) and HSP70(345-53)) are contained in the T cruzi HSP70 antigen. Indeed two of them (H5P70(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. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.