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

Research output: Contribution to journalArticleResearchpeer-review

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, Moran ; Farenc, Carine ; Mukhopadhyay, Madhura ; Jayasinghe, Dhilshan ; Decroos, Amandine ; Benati, Daniela ; Tan, Li Lynn ; Ciacchi, Lisa ; Reid, Hugh H ; Rossjohn, Jamie ; Chakrabarti, Lisa ; Gras, Stephanie. / CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers. In: Science Immunology. 2018 ; Vol. 3, No. 24.
@article{825812338b724fda8ea4a0967bdabc18,
title = "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.",
author = "Moran Galperin and Carine Farenc and Madhura Mukhopadhyay and Dhilshan Jayasinghe and Amandine Decroos and Daniela Benati and Tan, {Li Lynn} and Lisa Ciacchi and Reid, {Hugh H} and Jamie Rossjohn and Lisa Chakrabarti and Stephanie Gras",
year = "2018",
month = "6",
day = "8",
doi = "10.1126/sciimmunol.aat0687",
language = "English",
volume = "3",
journal = "Science Immunology",
issn = "2470-9468",
publisher = "American Association for the Advancement of Science",
number = "24",

}

Galperin, M, Farenc, C, Mukhopadhyay, M, Jayasinghe, D, Decroos, A, Benati, D, Tan, LL, Ciacchi, L, Reid, HH, Rossjohn, J, Chakrabarti, L & Gras, S 2018, 'CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers', Science Immunology, vol. 3, no. 24, eaat0687. https://doi.org/10.1126/sciimmunol.aat0687, https://doi.org/10.1126/sciimmunol.aat0687

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; Gras, Stephanie.

In: Science Immunology, Vol. 3, No. 24, eaat0687, 08.06.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers

AU - Galperin, Moran

AU - Farenc, Carine

AU - Mukhopadhyay, Madhura

AU - Jayasinghe, Dhilshan

AU - Decroos, Amandine

AU - Benati, Daniela

AU - Tan, Li Lynn

AU - Ciacchi, Lisa

AU - Reid, Hugh H

AU - Rossjohn, Jamie

AU - Chakrabarti, Lisa

AU - Gras, Stephanie

PY - 2018/6/8

Y1 - 2018/6/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85050016514&partnerID=8YFLogxK

U2 - 10.1126/sciimmunol.aat0687

DO - 10.1126/sciimmunol.aat0687

M3 - Article

VL - 3

JO - Science Immunology

JF - Science Immunology

SN - 2470-9468

IS - 24

M1 - eaat0687

ER -