2. Academic Validation
  3. CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers

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

  • Sci Immunol. 2018 Jun 8;3(24):eaat0687. doi: 10.1126/sciimmunol.aat0687.
Moran Galperin 1,  Carine Farenc 2,  Madhura Mukhopadhyay 1,  Dhilshan Jayasinghe 2,  Amandine Decroos 1,  Daniela Benati 1,  Li Lynn Tan 2,  Lisa Ciacchi 2,  Hugh H Reid 2 3,  Jamie Rossjohn 2 3 4,  Lisa A Chakrabarti 1 5,  Stephanie Gras 2 3
Affiliations

Affiliations

  • 1 Pasteur Institute, Viral Pathogenesis Unit, Paris, France.
  • 2 Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • 3 ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
  • 4 Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
  • 5 INSERM, U1108, Paris, France.
PMID: 29884618 DOI: 10.1126/sciimmunol.aat0687
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.

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