Identification of HLA-A02:01-restricted CTL epitopes in Trypanosoma cruzi heat shock protein-70 recognized by Chagas disease patients

• Published in: Microbes and infection 2011-11, Vol.13 (12-13), p.1025-1032
• Main Authors: MARANON, Concepción, EGUI, Adriana, CARRILERO, Bartolome, THOMAS, M. Carmen, PINAZO, M. Jesus, GASCON, Joaquim, SEGOVIA, Manuel, LOPEZ, Manuel Carlos
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Human protozoal diseases; Infectious diseases; Life cycle. Host-agent relationship. Pathogenesis; Medical sciences; Microbiology; Parasitic diseases; Protozoa; Protozoal diseases; Trypanosoma cruzi; Trypanosomiasis
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2011.05.010

CD8 super(+) 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 super(b) mice. Our results show that four immunodominant epitopes (HSP70 sub(210-8), HSP70 sub(255-63), HSP70 sub(316-24) and HSP70 sub(345-53)) are contained in the T. cruzi HSP70 antigen. Indeed two of them (HSP70 sub(210-8) and HSP70 sub(316-24)) were also recognized by CTL of HLA-A*02:01 super(+) 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[lowast]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 super(+) epitopes.