HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tzelepis, F. Articles by Rodrigues, M. M. Search for Related Content PubMed PubMed Citation Articles by Tzelepis, F. Articles by Rodrigues, M. M.

Infection with Trypanosoma cruzi Restricts the Repertoire of Parasite-Specific CD8⁺ T Cells Leading to Immunodominance¹

Fanny Tzelepis^*,, Bruna C. G. de Alencar^*,, Marcus L. O. Penido, Carla Claser^*,, Alexandre V. Machado^,¶, Oscar Bruna-Romero, Ricardo T. Gazzinelli^,¶ and Mauricio M. Rodrigues^2,*,

^* Centro Interdisciplinar de Terapia Gênica and Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; Departamento de Bioquímica e Imunologia and Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; and ^¶ Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), and The Millennium Institute for Vaccine Development and Technology (Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-420067/2005-1), Rede Mineira de Estrutura e Função de Biomoléculas (Fundação de Amparo à Pesquisa do Estado de Minas Gerais-24000). F.T., B.C.G.d.A., and C.C. are recipients of fellowships from FAPESP. A.V.M., O.B.-R., R.T.G., and M.M.R. are recipients of fellowships from CNPq.

² Address correspondence and reprint requests to Dr. Mauricio M. Rodrigues, Centro Interdisciplinar de Terapia Gênica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Mirassol, 207, São Paulo-SP, Brazil, 04044-010. E-mail address: mrodrigues{at}ecb.epm.br

³ Abbreviations used in this paper: MHC-I, MHC class I; TS, trans-sialidase; SFC, spot forming cell; ASP-2, amastigote surface protein 2.

This article has been cited by other articles:

				B. C. G. de Alencar, P. M. Persechini, F. A. Haolla, G. de Oliveira, J. C. Silverio, J. Lannes-Vieira, A. V. Machado, R. T. Gazzinelli, O. Bruna-Romero, and M. M. Rodrigues Perforin and Gamma Interferon Expression Are Required for CD4+ and CD8+ T-Cell-Dependent Protective Immunity against a Human Parasite, Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination Infect. Immun., October 1, 2009; 77(10): 4383 - 4395. [Abstract] [Full Text] [PDF]