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
| Autor: | Chiara Triulzi, Rebecca Voltan, Riccardo Gavioli, Indresh K. Srivastava, Aurelio Cafaro, Cinzia Fortini, Francesca Gagliardoni, Arianna Castaldello, Antonella Caputo, Barbara Ensoli, Susan W. Barnett, Eleonora Gallerani, Egidio Brocca Cofano, Silvia Cellini |
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| Rok vydání: | 2008 |
| Předmět: |
Cellular immunity
Subdominant Ovalbumin T cell AIDS Vaccine Tat Epitopes T-Lymphocyte HIV Envelope Protein gp120 Major histocompatibility complex Epitope NO Epitopes Mice Species Specificity Antigen medicine Animals Cells Cultured AIDS Vaccines General Veterinary General Immunology and Microbiology biology env Gene Products Human Immunodeficiency Virus Public Health Environmental and Occupational Health Th1 Cells biology.organism_classification Virology Mice Inbred C57BL CTL Infectious Diseases medicine.anatomical_structure Immunology Lentivirus HIV-1 biology.protein Molecular Medicine Immunization tat Gene Products Human Immunodeficiency Virus Spleen T-Lymphocytes Cytotoxic |
| Zdroj: | Vaccine. 26:727-737 |
| ISSN: | 0264-410X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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