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PDBsum entry 4f9l
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Immune system
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PDB id
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4f9l
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References listed in PDB file
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Key reference
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Title
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The molecular basis for modulation of human Vγ9Vδ2 t cell responses by cd277/butyrophilin-3 (btn3a)-Specific antibodies.
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Authors
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A.Palakodeti,
A.Sandstrom,
L.Sundaresan,
C.Harly,
S.Nedellec,
D.Olive,
E.Scotet,
M.Bonneville,
E.J.Adams.
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Ref.
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J Biol Chem, 2012,
287,
32780-32790.
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PubMed id
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Abstract
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Human Vγ9Vδ2 T cells are well known for their rapid and potent response to
infection and tumorigenesis when in the presence of endogenous or exogenous
phosphoisoprenoids. However, the molecular mechanisms behind the activation of
this γδ T cell population remains unclear. Evidence pointing to a role for the
CD277/butyrophilin-3 (BTN3A) molecules in this response led us to investigate
the structures of these molecules and their modifications upon binding to an
agonist antibody (20.1) that mimics phosphoisoprenoid-mediated Vγ9Vδ2
activation and an antagonist antibody (103.2) that inhibits this reactivity. We
find that the three BTN3A isoforms: BTN3A1, BTN3A2, and BTN3A3, have high
structural homology to the B7 superfamily of proteins and exist as V-shaped
homodimers in solution, associating through the membrane proximal C-type Ig
domain. The 20.1 and 103.2 antibodies bind to separate epitopes on the BTN3A
Ig-V domain with high affinity but likely with different valencies based on
their binding orientation. These structures directly complement functional
studies of this system that demonstrate that BTN3A1 is necessary for Vγ9Vδ2
activation and begin to unravel the extracellular events that occur during
stimulation through the Vγ9Vδ2 T cell receptor.
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