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 ORCID: https://orcid.org/0000-0002-2020-7522, Chakrabarti, Lisa A. and Gras, Stephanie 2018. CD4+ T cell–mediated HLA class II cross-restriction in HIV controllers. Science Immunology 3 (24) , eaat0687. 10.1126/sciimmunol.aat0687

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	American Association for the Advancement of Science
ISSN:	2470-9468
Date of First Compliant Deposit:	30 July 2018
Date of Acceptance:	18 April 2018
Last Modified:	27 Nov 2024 05:00
URI:	https://orca.cardiff.ac.uk/id/eprint/112932

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