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© Charles DAUGUET, Institut Pasteur
HIV particles
Scientific Fields
Diseases
Organisms
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Technique

About

Research thematic:  HIV immune control

Our research concerns the field of HIV pathogenesis, with an emphasis on the mechanisms that perturb CD4+ T cell responses and lead to the development of AIDS. The team currently focuses on the study of rare patients who spontaneously control of HIV replication in the absence of antiretroviral therapy. Such patients, called HIV Controllers or Elite Controllers, show signs of a particularly efficient antiviral immune response that contains HIV replication to very low levels. We have launched an in-depth characterization of HIV-specific CD4+ T cells in Controllers, to understand how such cells could escape depletion and maintain efficient helper function.

We obtained evidence for the persistence of highly differentiated Th1 effectors CD4+ T cells, in Controllers, while such cells were lost in patients treated in the long-term. The presence of Th1 effectors in Controlers was unexpected considering the very low levels of viral antigens available to stimulate effector responses. MHC class II tetramer binding analyses revealed that Controller CD4+ T cells expressed T cell receptors (TCRs) with a high avidity for immunodominant HIV Gag peptides, while such cells were absent from treated patients. Thus, HIV controllers harbored a pool of memory CD4+ T cells with the intrinsic ability to detect minimal amounts of viral antigens, and to receive sufficient signal to undergo effector differentiation. These high avidity CD4+ T cells may maintain the immune system of HIV Controllers in constant alert, and allow the triggering of a very rapid antiviral response in case of a rebound in viral replication.

To analyze the molecular determinants of this sensitive antiviral response, we have analyzed the repertoire of TCRs expressed by CD4+ T cells specific for the most immunodominant epitope in HIV Gag. We obtained evidence that particular TCRs are associated with HIV control. These shared (or “public”) TCRs are preferentially expressed by Controller CD4+ T cells and show remarkably high affinity for the Gag peptide/MHC II complex. When transferred into healthy donor cells with lentivectors, these public TCRs confer a series of properties characteristic of Controller CD4+ T cell responses, including high antigen sensitivity and polyfunctionality. These findings suggest it may be beneficial to induce the amplification of such TCRs in vaccination and immunotherapeutic approaches directed at containing HIV infection.

fig2-avidity-v3-edited

Events

GRS (Groupe de Reflexion SIDA) meeting: “Residual risk of HIV sexual transmission”

Building: Lwoff – Room: Room 14 , ground floor – Address: Institut Pasteur, Rue du Docteur Roux, Paris, France
2017-04-18 16:00:00 2017-04-18 18:00:00 Europe/Paris GRS (Groupe de Reflexion SIDA) meeting: “Residual risk of HIV sexual transmission” Speakers : Romulus BREBAN, Jade GHOSN ,   Nathalie DEJUCQ —————- Romulus BREBAN Unité d’Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris Meta-analysis of the residual risk of sexual HIV transmission from efficiently treated persons     […] Institut Pasteur, Rue du Docteur Roux, Paris, France

Groupe de Réflexion SIDA (GRS) meeting: “HIV vaccination strategies”

Building: Lwoff – Room: 14 RdC – Address: 28 Rue du Dr Roux, 75015 Paris, France
2017-11-21 16:00:00 2017-11-21 18:00:00 Europe/Paris Groupe de Réflexion SIDA (GRS) meeting: “HIV vaccination strategies” Organizer:  Lisa CHAKRABARTI, for the GRS organization committee Unité de Pathogénie Virale, Institut Pasteur, Paris   Speakers :  Frédéric TANGY Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris Protective efficacy of live measles-HIV vaccine […] 28 Rue du Dr Roux, 75015 Paris, France

Projects

Publications