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PDBsum entry 4ozh
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Immune system
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PDB id
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4ozh
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Contents |
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181 a.a.
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181 a.a.
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195 a.a.
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240 a.a.
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12 a.a.
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13 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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T-Cell receptor recognition of hla-Dq2-Gliadin complexes associated with celiac disease.
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Authors
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J.Petersen,
V.Montserrat,
J.R.Mujico,
K.L.Loh,
D.X.Beringer,
M.Van lummel,
A.Thompson,
M.L.Mearin,
J.Schweizer,
Y.Kooy-Winkelaar,
J.Van bergen,
J.W.Drijfhout,
W.T.Kan,
N.L.La gruta,
R.P.Anderson,
H.H.Reid,
F.Koning,
J.Rossjohn.
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Ref.
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Nat Struct Biol, 2014,
21,
480-488.
[DOI no: ]
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PubMed id
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Abstract
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Celiac disease is a T cell-mediated disease induced by dietary gluten, a
component of which is gliadin. 95% of individuals with celiac disease carry the
HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor
(TCR) usage and fine specificity of patient-derived T-cell clones specific for
two epitopes from wheat gliadin, DQ2.5-glia-α1a and DQ2.5-glia-α2. We
determined the ternary structures of four distinct biased TCRs specific for
those epitopes. All three TCRs specific for DQ2.5-glia-α2 docked centrally
above HLA-DQ2, which together with mutagenesis and affinity measurements
provided a basis for the biased TCR usage. A non-germline encoded arginine
residue within the CDR3β loop acted as the lynchpin within this common docking
footprint. Although the TCRs specific for DQ2.5-glia-α1a and DQ2.5-glia-α2
docked similarly, their interactions with the respective gliadin determinants
differed markedly, thereby providing a basis for epitope specificity.
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