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

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

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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.

Original languageEnglish
Article numbereaat0687
Number of pages13
JournalScience Immunology
Volume3
Issue number24
DOIs
Publication statusPublished - 8 Jun 2018

Cite this

Galperin, M., Farenc, C., Mukhopadhyay, M., Jayasinghe, D., Decroos, A., Benati, D., Tan, L. L., Ciacchi, L., Reid, H. H., Rossjohn, J., Chakrabarti, L., & Gras, S. (2018). CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers. Science Immunology, 3(24), [eaat0687]. https://doi.org/10.1126/sciimmunol.aat0687