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

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Galperin, Moran | Farenc, Carine | Mukhopadhyay, Madhura | Jayasinghe, Dhilshan | Decroos, Amandine | Benati, Daniela | Tan, Li Lynn | Ciacchi, Lisa | Reid, Hugh, H | Rossjohn, Jamie | Chakrabarti, Lisa, A. | Gras, Stéphanie

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. 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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