title: Transfer of the ability of HIV-1 Tat to raise an adjuvant-free humoral immune response to unrelated antigens.
abstract: The HIV-1 Tat protein is able to raise a humoral immune response in the absence of adjuvant. Here, we investigated whether this property can be transferred to unrelated antigens. We first observed that Tat self-adjuvanticity is a T cell-dependent phenomenon in which a Th2 profile predominates. Then, we showed that the determinant governing the property is located in the region 1-57 of Tat and that fragment Tat1-57 can make two unrelated model antigens immunogenic in the absence of adjuvant. We found a Th2 pattern of immune response for both antigens, suggesting that Tat1-57 mediates this response. Next, we showed that, although less efficient than Tat1-57, the Tat37-57 fragment suffices to transfer the adjuvant property to other antigens. We also observed that preservation of cysteine 37 is absolutely required for the transfer, suggesting the role of disulphide-mediated dimerization in the transfer of the adjuvant property. Our observations suggest that for various antigens, the use of Tat37-57 or Tat1-57 or Tat22-57C(22-34)A might represent an alternative to adjuvants in humans, thereby opening up new perspectives in vaccination.
authors.affiliation: The CEA, Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut de Biologie et Technologies de Saclay, Service de Pharmacologie et d'Immunoanalyse, Laboratoire d'Ingénierie des Anticorps pour la Santé, Gif-Sur-Yvette, F-91191 France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Gadzinski
authors.forename: Delphine
authors.initials: D
authors.lastname: Matz
authors.forename: Emilie
authors.initials: E
authors.lastname: Favre
authors.forename: Michel
authors.initials: M
authors.lastname: Léonetti
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000941:Antigens / Q000276:immunology*; D004252:DNA Mutational Analysis; D005260:Female; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D054322:tat Gene Products, Human Immunodeficiency Virus