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PDBsum entry 4z7v
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Immune system
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PDB id
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4z7v
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Contents |
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180 a.a.
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172 a.a.
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199 a.a.
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243 a.a.
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13 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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L3-12 complex
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Structure:
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Mhc class ii hla-dq-alpha chain. Chain: a, c. Fragment: unp residues 1-184. Engineered: yes. Mhc class ii hla-dq-beta-1. Chain: b, d. Fragment: unp residues 1-192. Engineered: yes. T-cell receptor, l3-12 alpha chain.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dqa1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: hla-dqb1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
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Resolution:
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2.65Å
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R-factor:
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0.189
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R-free:
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0.226
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Authors:
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J.Petersen,J.Rossjohn,H.H.Reid,F.Koning
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Key ref:
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J.Petersen
et al.
(2015).
Determinants of gliadin-specific T cell selection in celiac disease.
J Immunol,
194,
6112-6122.
PubMed id:
DOI:
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Date:
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08-Apr-15
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Release date:
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03-Jun-15
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PROCHECK
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Headers
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References
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Q30069
(Q30069_HUMAN) -
MHC class II HLA-DQ-alpha chain (Fragment) from Homo sapiens
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Seq:
Struc:
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227 a.a.
180 a.a.
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O19707
(O19707_HUMAN) -
MHC class II HLA-DQ-beta-1 (Fragment) from Homo sapiens
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Seq:
Struc:
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229 a.a.
172 a.a.
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No UniProt id for this chain
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DOI no:
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J Immunol
194:6112-6122
(2015)
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PubMed id:
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Determinants of gliadin-specific T cell selection in celiac disease.
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J.Petersen,
J.van Bergen,
K.L.Loh,
Y.Kooy-Winkelaar,
D.X.Beringer,
A.Thompson,
S.F.Bakker,
C.J.Mulder,
K.Ladell,
J.E.McLaren,
D.A.Price,
J.Rossjohn,
H.H.Reid,
F.Koning.
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ABSTRACT
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In HLA-DQ8-associated celiac disease (CD), the pathogenic T cell response is
directed toward an immunodominant α-gliadin-derived peptide (DQ8-glia-α1).
However, our knowledge of TCR gene usage within the primary intestinal tissue of
HLA-DQ8 (+) CD patients is limited. We identified two populations of
HLA-DQ8-glia-α1 tetramer(+) CD4(+) T cells that were essentially undetectable
in biopsy samples from patients on a gluten-free diet but expanded rapidly and
specifically after antigenic stimulation. Distinguished by expression of TRBV9,
both T cell populations displayed biased clonotypic repertoires and reacted
similarly against HLA-DQ8-glia-α1. In particular, TRBV9 paired most often with
TRAV26-2, whereas the majority of TRBV9(-) TCRs used TRBV6-1 with no clear TRAV
gene preference. Strikingly, both tetramer(+)/TRBV9(+) and tetramer(+)/TRBV9(-)
T cells possessed a non-germline-encoded arginine residue in their CDR3α and
CDR3β loops, respectively. Comparison of the crystal structures of three
TRBV9(+) TCRs and a TRBV9(-) TCR revealed that, as a result of distinct TCR
docking modes, the HLA-DQ8-glia-α1 contacts mediated by the CDR3-encoded
arginine were almost identical between TRBV9(+) and TRBV9(-) TCRs. In all cases,
this interaction centered on two hydrogen bonds with a specific serine residue
in the bound peptide. Replacement of serine with alanine at this position
abrogated TRBV9(+) and TRBV9(-) clonal T cell proliferation in response to
HLA-DQ8-glia-α1. Gluten-specific memory CD4(+) T cells with structurally and
functionally conserved TCRs therefore predominate in the disease-affected tissue
of patients with HLA-DQ8-mediated CD.
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