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PDBsum entry 4p4k
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Immune system
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PDB id
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4p4k
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Contents |
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178 a.a.
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199 a.a.
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204 a.a.
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241 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.
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Authors
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G.M.Clayton,
Y.Wang,
F.Crawford,
A.Novikov,
B.T.Wimberly,
J.S.Kieft,
M.T.Falta,
N.A.Bowerman,
P.Marrack,
A.P.Fontenot,
S.Dai,
J.W.Kappler.
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Ref.
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Cell, 2014,
158,
132-142.
[DOI no: ]
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PubMed id
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Abstract
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T-cell-mediated hypersensitivity to metal cations is common in humans. How the
T cell antigen receptor (TCR) recognizes these cations bound to a major
histocompatibility complex (MHC) protein and self-peptide is unknown.
Individuals carrying the MHCII allele, HLA-DP2, are at risk for chronic
beryllium disease (CBD), a debilitating inflammatory lung condition caused by
the reaction of CD4 T cells to inhaled beryllium. Here, we show that the
T cell ligand is created when a Be(2+) cation becomes buried in an
HLA-DP2/peptide complex, where it is coordinated by both MHC and peptide acidic
amino acids. Surprisingly, the TCR does not interact with the Be(2+) itself, but
rather with surface changes induced by the firmly bound Be(2+) and an
accompanying Na(+) cation. Thus, CBD, by creating a new antigen by indirectly
modifying the structure of preexisting self MHC-peptide complex, lies on the
border between allergic hypersensitivity and autoimmunity.
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