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Etude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : Implications dans l'immunogénicité de protéines et applications potentielles en vaccination

Abstract : Soluble proteins are usually poorly immunogenic, which is a limit to the development of subunit vaccines based on proteins. My thesis work aimed to decipher some molecular and cellular mechanisms that contribute to the immunogenicity and to exploit them to develop innovative approaches to improve the ability of proteins to trigger the immune response. For this purpose, I mainly used the transcriptional transactivator (Tat) of HIV-1. I showed that the oligomerization of Tat enables a B-TH-2 collaborative mechanism to induce the immune response in the absence of adjuvant. I identified the minimum region determining the effect and showed that it confers the self-adjuvanting property to other antigens. In the second part of my work, I showed that the MHC I and MHC II restricted presentation to T cells is increased when the proteins are endowed with the ability to bind ubiquitous sulfated polysaccharides: heparan sulfates. This work helped to define new approaches to improve the immunogenicity of proteins that are likely to be included in vaccine preparations.
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https://theses.hal.science/tel-00711758
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Submitted on : Monday, June 25, 2012 - 3:57:35 PM
Last modification on : Wednesday, November 29, 2017 - 3:02:27 PM
Long-term archiving on: : Wednesday, September 26, 2012 - 2:55:37 AM

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  • HAL Id : tel-00711758, version 1

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Adeline Gadzinski. Etude de la propriété adjuvante de la protéine Tat du VIH-1 et utilisation de sa capacité à lier les héparanes sulfates pour évaluer le rôle de cibles ubiquitaires dans les mécanismes de présentation antigénique : Implications dans l'immunogénicité de protéines et applications potentielles en vaccination. Immunologie. Université Paris Sud - Paris XI, 2011. Français. ⟨NNT : ⟩. ⟨tel-00711758⟩

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