Journal
SCIENCE IMMUNOLOGY
Volume 3, Issue 24, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aat0687
Keywords
-
Categories
Funding
- Sidaction [AI25-1-02345]
- Agence Nationale de Recherche sur le SIDA et les Hepatites Virales [ANRS 16186]
- Agence Nationale de la Recherche [ANR 14 CE16]
- ANR
- ANRS
- Australian Research Council (ARC)
- National Health and Medical Research Council [GNT1106756]
- ARC Laureate Fellowship
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available