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.
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.
Gavioli
Riccardo
R
Department of Biochemistry and Molecular Biology, Via L. Borsari 46, University of Ferrara, 44100 Ferrara, Italy. r.gavioli@unife.it <r.gavioli@unife.it>
Cellini
Silvia
S
Castaldello
Arianna
A
Voltan
Rebecca
R
Gallerani
Eleonora
E
Gagliardoni
Francesca
F
Fortini
Cinzia
C
Cofano
Egidio Brocca
EB
Triulzi
Chiara
C
Cafaro
Aurelio
A
Srivastava
Indresh
I
Barnett
Susan
S
Caputo
Antonella
A
Ensoli
Barbara
B
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification
D016915:AIDS Vaccines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus; D010047:Ovalbumin