Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8678

Type
Article
Copyright
Open access
Collections
Share

Statistics
Metadata
Show full item record

SUBDOMINANT/CRYPTIC CD8 T CELL EPITOPES CONTRIBUTE TO RESISTANCE AGAINST EXPERIMENTAL INFECTION WITH A HUMAN PROTOZOAN PARASITE
Dominguez, Mariana Ribeiro et al. | Date Issued: 2011
Author
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
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
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
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
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
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
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil
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 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
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.
Keywords
Cell-mediated immunity
Immune response
Protozoan infections
Trypanosoma cruzi/vaccination and immunity
 
Publisher
Public Library of Science
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
DOI
10.1371/journal.pone.0022011
ISSN
1932-6203