The Tat protein broadens T cell responses directed to the HIV-1 antigens Gag and Env: implications for the design of new vaccination strategies against AIDS.
Vaccine
; 26(5): 727-37, 2008 Jan 30.
Article
em En
| MEDLINE
| ID: mdl-18096278
ABSTRACT
We have previously shown that the biologically active Tat protein targets and efficiently enters dendritic cells, and increases the proteolytic activities of the immunoproteasome, thereby favoring the generation and presentation of the subdominant MHC-I binding CTL epitopes of heterologous antigens. In the present study, we demonstrate that Tat broadens in vivo epitope-specific T cell responses directed to heterologous antigens including HIV structural proteins. Specifically, co-immunization of mice with OVA and Tat proteins induces CTL responses against subdominant and cryptic OVA-derived epitopes, which are not detected in mice vaccinated with OVA alone. Similarly, mice vaccinated with the HIV-1 Gag, Env or V2-deleted Env antigens in combination with Tat show Th1-type and CTL responses directed to a larger number of T cell epitopes, as compared to mice vaccinated with these proteins in absence of Tat. In contrast, Tat did not affect Th2-type responses to these structural HIV proteins. These results indicate that Tat is not only an antigen but also a novel Th1-type adjuvant capable of broadening in vivo the spectrum of epitopes recognized by T cells, and suggest that Tat can be considered an optimal co-antigen in the development of novel vaccination strategies against AIDS.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
/
Proteína gp120 do Envelope de HIV
/
HIV-1
/
Imunização
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Vacinas contra a AIDS
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Produtos do Gene tat do Vírus da Imunodeficiência Humana
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Produtos do Gene env do Vírus da Imunodeficiência Humana
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article