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CD4 + T cell–mediated HLA class II cross-restriction in HIV controllers

Abstract : Rare individuals, termed HIV controllers, spontaneously control HIV infection by mounting efficient T cell responses against the virus. Protective CD4+ T cell responses from HIV controllers involve high-affinity public T cell receptors (TCRs) recognizing an immunodominant capsid epitope (Gag293) presented by a remarkably broad array of human leukocyte antigen (HLA) class II molecules. Here, we determine the structures of a prototypical public TCR bound to HLA-DR1, HLA-DR11, and HLA-DR15 molecules presenting the Gag293 epitope. TCR recognition was driven by contacts with the Gag293 epitope, a feature that underpinned the extensive HLA cross-restriction. These high-affinity TCRs promoted mature immunological synapse formation and cytotoxic capacity in both CD4+ and CD8+ T cells. The public TCRs suppressed HIV replication in multiple genetic backgrounds ex vivo, emphasizing the functional advantage conferred by broad HLA class II cross-restriction.
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Submitted on : Friday, May 17, 2019 - 11:34:43 AM
Last modification on : Monday, January 13, 2020 - 5:08:16 PM

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Moran Galperin, Carine Farenc, Madhura Mukhopadhyay, Dhilshan Jayasinghe, Amandine Decroos, et al.. CD4 + T cell–mediated HLA class II cross-restriction in HIV controllers. Science Immunology, American Association for the Advancement of Science, 2018, 3 (24), pp.eaat0687. ⟨10.1126/sciimmunol.aat0687⟩. ⟨pasteur-02132543⟩

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