Transfer of the ability of HIV-1 Tat to raise an adjuvant-free humoral immune response to unrelated antigens
- 作者：Adeline Gadzinski ; Delphine Matz ; Emilie Favre ; Michel Lé ; onetti ; michel.leonetti@cea.fr
- 关键词：Tat ; Transcriptional transactivator ; HIV ; human immunodeficiency virus ; BCR ; B cell receptor ; TLR ; toll-like receptor ; KO ; knock-out ; SFC ; spot-forming cell
- 刊名：Vaccine
- 出版年：2012
- 期刊代码：89_0264410x
- 类别：imm
- 出版时间：16 April, 2012
- 卷：30
- 期：18
- 页码：2859-2868
- 文件大小：635 K
摘要
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.