title: Infection with Trypanosoma cruzi restricts the repertoire of parasite-specific CD8+ T cells leading to immunodominance.
abstract: Interference or competition between CD8(+) T cells restricted by distinct MHC-I molecules can be a powerful means to establish an immunodominant response. However, its importance during infections is still questionable. In this study, we describe that following infection of mice with the human pathogen Trypanosoma cruzi, an immunodominant CD8(+) T cell immune response is developed directed to an H-2K(b)-restricted epitope expressed by members of the trans-sialidase family of surface proteins. To determine whether this immunodominance was exerted over other non-H-2K(b)-restricted epitopes, we measured during infection of heterozygote mice, immune responses to three distinct epitopes, all expressed by members of the trans-sialidase family, recognized by H-2K(b)-, H-2K(k)-, or H-2K(d)-restricted CD8(+) T cells. Infected heterozygote or homozygote mice displayed comparably strong immune responses to the H-2K(b)-restricted immunodominant epitope. In contrast, H-2K(k)- or H-2K(d)-restricted immune responses were significantly impaired in heterozygote infected mice when compared with homozygote ones. This interference was not dependent on the dose of parasite or the timing of infection. Also, it was not seen in heterozygote mice immunized with recombinant adenoviruses expressing T. cruzi Ags. Finally, we observed that the immunodominance was circumvented by concomitant infection with two T. cruzi strains containing distinct immunodominant epitopes, suggesting that the operating mechanism most likely involves competition of T cells for limiting APCs. This type of interference never described during infection with a human parasite may represent a sophisticated strategy to restrict priming of CD8(+) T cells of distinct specificities, avoiding complete pathogen elimination by host effector cells, and thus favoring host parasitism.
authors.affiliation: Centro Interdisciplinar de Terapia Gênica and Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirasol 207, São Paulo, Brazil.
authors.forename: Fanny
authors.initials: F
authors.lastname: Tzelepis
authors.forename: Bruna C G
authors.initials: BC
authors.lastname: de Alencar
authors.forename: Marcus L O
authors.initials: ML
authors.lastname: Penido
authors.forename: Carla
authors.initials: C
authors.lastname: Claser
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Machado
authors.forename: Oscar
authors.initials: O
authors.lastname: Bruna-Romero
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology*; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006579:Heterozygote; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016056:Immunodominant Epitopes