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Study of molecular and cellular basis of the control of specific T CD8+ lymphocyte immunodominant immune response during experimental infection with Trypanosoma cruzi or recombinant adenoviruses immunization

Grant number: 10/09361-8
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): August 01, 2010
Effective date (End): July 31, 2015
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Jose Ronnie Carvalho de Vasconcelos
Grantee:Jonatan Ersching
Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


CD8+ T lymphocytes, critical components of the immune response to intracellular pathogens, focus their response on a few epitopes, even during infection by complex microorganisms. In this phenomen, so called immunodominance, the lymphocyte immune response specific to different epitopes is hierarchically organized. Recently, our team provided evidence of a critical difference between CD8+ T cell immunodominance elicited by recombinant human adenovirus type 5 immunization and infection by the intracellular parasite Trypanosoma cruzi, agent of Chagas Disease. Whereas the first elicit immune response specific to several epitopes from the recombinant protein ASP-2 (Amastigote Surface Protein-2), the latter restricts this response to one epitope from the same protein. The nature of this control remains elusive, but it is reasonable to state that it occur on the level of the APC (Antigen Presenting Cell) during the activation of specific T cells. Based on this hypothesis, this project is aimed at characterizing and comparing the antigen presentation of MHC I-restricted epitopes during recombinant adenoviruses immunization and T. cruzi infection. Thus, we expect to determine specific cellular and molecular factors responsible for the CD8+ T cell immunodominance pattern to T. cruzi epitopes. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ERSCHING, JONATAN; VASCONCELOS, JOSE R.; FERREIRA, CAMILA P.; CAETANO, BRAULIA C.; MACHADO, ALEXANDRE V.; BRUNA-ROMERO, OSCAR; BARON, MONIQUE A.; FERREIRA, LUDMILA R. P.; CUNHA-NETO, EDECIO; ROCK, KENNETH L.; et al. The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8(+) T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi. PLOS PATHOGENS, v. 12, n. 4, . (15/08814-2, 12/22514-3, 10/09361-8, 09/06820-4)

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