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Sci Immunol. 2018 Jun 8;3(24). pii: eaat0687. doi: 10.1126/sciimmunol.aat0687.

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

Author information

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.

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.

PMID:
29884618
DOI:
10.1126/sciimmunol.aat0687
[Indexed for MEDLINE]

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