Importance of the response to subdominant epitope, proliferation and recirculation of CD8+ T lymphocytes during experimental vaccination against Trypanosoma cruzi infection.

Author(s)

Mariana Ribeiro Dominguez

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2013-11-14

Examining board members

Mauricio Martins Rodrigues; Maria Bellio; Jose Maria Alvarez Mosig; Paula Ordonhez Rigato; Oscar Bruna Romero

• Advisor: Mauricio Martins Rodrigues

Abstract

In the present study, we evaluated the impact of the immune response to sub-dominant CD8 epitopes on immunity generated by genetic vaccination. During experimental infection only a single dominant epitope is recognized on the antigen ASP-2. In contrast, the CD8+ T lymphocytes induced in animals genetically vaccinated with ASP-2 recognized, in addition to the dominant epitope, two other epitopes (sub-dominants). The identification of these epitopes allowed us to test the role of immune response to sub-dominant epitopes in protective immunity. After genetic vaccination with ASP-2 mutated gene, without the response to dominant epitope, we concluded that the immune response to the sub-dominant epitopes can be important to protective immunity. In spite of the critical role of CD8+ T lymphocytes in protective immune response induced by genetic vaccination using the heterologous prime-boost regimen, it is unclear whether after the experimental challenge these CD8+ T lymphocytes need to proliferate or recirculate to mediate protective immunity. Our results challenge the paradigm of action of traditional vaccines that immunity is dependent on the proliferation of memory T lymphocytes and that these cells do not need to recirculate. (AU)

• FAPESP's process: 09/02194-1 - Generation and analysis of the immunogecity of plasmids containing subdominant CD8 epitopes expressed in Trypanosoma cruzi
• Grantee: Mariana Ribeiro Dominguez
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)