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.

CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers / 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, Stephanie. - In: SCIENCE IMMUNOLOGY. - ISSN 2470-9468. - 3:24(2018), pp. N/A-N/A. [10.1126/sciimmunol.aat0687]

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

Benati, Daniela;
2018

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.
2018
3
24
N/A
N/A
CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers / 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, Stephanie. - In: SCIENCE IMMUNOLOGY. - ISSN 2470-9468. - 3:24(2018), pp. N/A-N/A. [10.1126/sciimmunol.aat0687]
Galperin, Moran; Farenc, Carine; Mukhopadhyay, Madhura; Jayasinghe, Dhilshan; Decroos, Amandine; Benati, Daniela; Tan, Li Lynn; Ciacchi, Lisa; Reid, H...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1169081
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