| Author | Dominguez, Mariana Ribeiro | |
| Author | Silveira, Eduardo L. V. | |
| Author | Vasconcelos, José Ronnie C. de | |
| Author | Bargieri, Bruna Cunha de Alencar | |
| Author | Rodrigues, Mauricio M. | |
| Author | Machado, Alexandre Vieira | |
| Author | Bruna-Romero, Oscar | |
| Author | Gazzinelli, Ricardo Tostes | |
| Access date | 2014-10-27T15:51:09Z | |
| Available date | 2014-10-27T15:51:09Z | |
| Document date | 2011 | |
| Citation | Dominguez, Mariana Ribeiro et al. Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite. PLoS One, 6(7): e22011, 2011 | pt_BR |
| ISSN | 1932-6203 | |
| URI | https://www.arca.fiocruz.br/handle/icict/8678 | |
| Sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo, The National Institute for Vaccine Technology, The Millennium Institute for Vaccine Development and Technology and The Millennium Institute for Gene Therapy, CNPq. | pt_BR |
| Language | eng | pt_BR |
| Publisher | Public Library of Science | pt_BR |
| Rights | open access | pt_BR |
| Title | Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1371/journal.pone.0022011 | |
| Abstract | During adaptive immune response, pathogen-specific CD8+ T cells recognize preferentially a small number of epitopes, a phenomenon known as immunodominance. Its biological implications during natural or vaccine-induced immune responses are still unclear. Earlier, we have shown that during experimental infection, the human intracellular pathogen Trypanosoma cruzi restricts the repertoire of CD8+ T cells generating strong immunodominance. We hypothesized that this phenomenon could be a mechanism used by the parasite to reduce the breath and magnitude of the immune response, favoring parasitism, and thus that artificially broadening the T cell repertoire could favor the host. Here, we confirmed our previous observation by showing that CD8+ T cells of H-2a infected mice recognized a single epitope of an immunodominant antigen of the trans-sialidase super-family. In sharp contrast, CD8+ T cells from mice immunized with recombinant genetic vaccines (plasmid DNA and adenovirus) expressing this same T. cruzi antigen recognized, in addition to the immunodominant epitope, two other subdominant epitopes. This unexpected observation allowed us to test the protective role of the immune response to subdominant epitopes. This was accomplished by genetic vaccination of mice with mutated genes that did not express a functional immunodominant epitope. We found that these mice developed immune responses directed solely to the subdominant/cryptic CD8 T cell epitopes and a significant degree of protective immunity against infection mediated by CD8+ T cells. We concluded that artificially broadening the T cell repertoire contributes to host resistance against infection, a finding that has implications for the host-parasite relationship and vaccine development. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Centro de Terapia Celular e Molecular São Paulo, SP, Brazil/Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/University of Massachusetts Medical School. Department of Medicine. Division of Infectious Disease and Immunology. Worcester, MA, United States of America | pt_BR |
| Subject | Cell-mediated immunity | pt_BR |
| Subject | Immune response | pt_BR |
| Subject | Protozoan infections | pt_BR |
| Subject | Trypanosoma cruzi/vaccination and immunity | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
