Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2011 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/8678 |
Resumo: | 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. |
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Dominguez, Mariana RibeiroSilveira, Eduardo L. V.Vasconcelos, José Ronnie C. deBargieri, Bruna Cunha de AlencarRodrigues, Mauricio M.Machado, Alexandre VieiraBruna-Romero, OscarGazzinelli, Ricardo Tostes2014-10-27T15:51:09Z2014-10-27T15:51:09Z2011Dominguez, 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, 20111932-6203https://www.arca.fiocruz.br/handle/icict/867810.1371/journal.pone.0022011Fundação 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.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, BrazilUniversidade 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, BrazilUniversidade 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, BrazilUniversidade 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, BrazilUniversidade 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, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, BrazilUniversidade 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 AmericaDuring 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.engPublic Library of ScienceSubdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasiteinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCell-mediated immunityImmune responseProtozoan infectionsTrypanosoma cruzi/vaccination and immunityinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8678/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALSubdominant.pdfSubdominant.pdfapplication/pdf933708https://www.arca.fiocruz.br/bitstream/icict/8678/2/Subdominant.pdf056c1f4bb5d2ab02c59a5d7218907b0bMD52TEXTSubdominant.pdf.txtSubdominant.pdf.txtExtracted texttext/plain59532https://www.arca.fiocruz.br/bitstream/icict/8678/3/Subdominant.pdf.txt300f2872a1a9c58c1fb34882b7af5dabMD53icict/86782019-06-19 10:13:23.86oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:13:23Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite |
| title |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite |
| spellingShingle |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite Dominguez, Mariana Ribeiro Cell-mediated immunity Immune response Protozoan infections Trypanosoma cruzi/vaccination and immunity |
| title_short |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite |
| title_full |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite |
| title_fullStr |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite |
| title_full_unstemmed |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite |
| title_sort |
Subdominant/cryptic CD8 T cell epitopes contribute to resistance against experimental infection with a human protozoan parasite |
| author |
Dominguez, Mariana Ribeiro |
| author_facet |
Dominguez, Mariana Ribeiro Silveira, Eduardo L. V. Vasconcelos, José Ronnie C. de Bargieri, Bruna Cunha de Alencar Rodrigues, Mauricio M. Machado, Alexandre Vieira Bruna-Romero, Oscar Gazzinelli, Ricardo Tostes |
| author_role |
author |
| author2 |
Silveira, Eduardo L. V. Vasconcelos, José Ronnie C. de Bargieri, Bruna Cunha de Alencar Rodrigues, Mauricio M. Machado, Alexandre Vieira Bruna-Romero, Oscar Gazzinelli, Ricardo Tostes |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Dominguez, Mariana Ribeiro Silveira, Eduardo L. V. Vasconcelos, José Ronnie C. de Bargieri, Bruna Cunha de Alencar Rodrigues, Mauricio M. Machado, Alexandre Vieira Bruna-Romero, Oscar Gazzinelli, Ricardo Tostes |
| dc.subject.en.pt_BR.fl_str_mv |
Cell-mediated immunity Immune response Protozoan infections Trypanosoma cruzi/vaccination and immunity |
| topic |
Cell-mediated immunity Immune response Protozoan infections Trypanosoma cruzi/vaccination and immunity |
| description |
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. |
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2011 |
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2011 |
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2014-10-27T15:51:09Z |
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2014-10-27T15:51:09Z |
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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 |
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10.1371/journal.pone.0022011 |
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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 1932-6203 10.1371/journal.pone.0022011 |
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