PMID- 23063329
OWN - NLM
STAT- MEDLINE
DCOM- 20121227
LR  - 20121022
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Linking)
VI  - 37
IP  - 4
DP  - 2012 Oct 19
TI  - Biased T cell receptor usage directed against human leukocyte antigen 
      DQ8-restricted gliadin peptides is associated with celiac disease.
PG  - 611-21
LID - S1074-7613(12)00419-0 [pii]
LID - 10.1016/j.immuni.2012.07.013 [doi]
AB  - Celiac disease is a human leukocyte antigen (HLA)-DQ2- and/or DQ8-associated T 
      cell-mediated disorder that is induced by dietary gluten. Although it is 
      established how gluten peptides bind HLA-DQ8 and HLA-DQ2, it is unclear how such 
      peptide-HLA complexes are engaged by the T cell receptor (TCR), a recognition 
      event that triggers disease pathology. We show that biased TCR usage (TRBV9( *)01) 
      underpins the recognition of HLA-DQ8-alpha-I-gliadin. The structure of a prototypical 
      TRBV9( *)01-TCR-HLA-DQ8-alpha-I-gliadin complex shows that the TCR docks centrally 
      above HLA-DQ8-alpha-I-gliadin, in which all complementarity-determining region-beta 
      (CDRbeta) loops interact with the gliadin peptide. Mutagenesis at the 
      TRBV9( *)01-TCR-HLA-DQ8-alpha-I-gliadin interface provides an energetic basis for the 
      Vbeta bias. Moreover, CDR3 diversity accounts for TRBV9( *)01(+) TCRs exhibiting 
      differing reactivities toward the gliadin epitopes at various deamidation states. 
      Accordingly, biased TCR usage is an important factor in the pathogenesis of 
      DQ8-mediated celiac disease.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Broughton, Sophie E
AU  - Broughton SE
AD  - The Department of Biochemistry and Molecular Biology, School of Biomedical 
      Sciences, Monash University, Clayton, Victoria, Australia.
FAU - Petersen, Jan
AU  - Petersen J
FAU - Theodossis, Alex
AU  - Theodossis A
FAU - Scally, Stephen W
AU  - Scally SW
FAU - Loh, Khai Lee
AU  - Loh KL
FAU - Thompson, Allan
AU  - Thompson A
FAU - van Bergen, Jeroen
AU  - van Bergen J
FAU - Kooy-Winkelaar, Yvonne
AU  - Kooy-Winkelaar Y
FAU - Henderson, Kate N
AU  - Henderson KN
FAU - Beddoe, Travis
AU  - Beddoe T
FAU - Tye-Din, Jason A
AU  - Tye-Din JA
FAU - Mannering, Stuart I
AU  - Mannering SI
FAU - Purcell, Anthony W
AU  - Purcell AW
FAU - McCluskey, James
AU  - McCluskey J
FAU - Anderson, Robert P
AU  - Anderson RP
FAU - Koning, Frits
AU  - Koning F
FAU - Reid, Hugh H
AU  - Reid HH
FAU - Rossjohn, Jamie
AU  - Rossjohn J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121011
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 9007-90-3 (Gliadin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Celiac Disease/*immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Gliadin/*immunology
MH  - HLA-DQ Antigens/chemistry/*immunology
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Peptide Fragments/immunology
MH  - Protein Interaction Domains and Motifs
MH  - Receptors, Antigen, T-Cell/chemistry/*immunology
EDAT- 2012/10/16 06:00
MHDA- 2012/12/28 06:00
CRDT- 2012/10/16 06:00
PHST- 2011/08/17 00:00 [received]
PHST- 2012/07/10 00:00 [accepted]
PHST- 2012/10/16 06:00 [entrez]
PHST- 2012/10/16 06:00 [pubmed]
PHST- 2012/12/28 06:00 [medline]
AID - S1074-7613(12)00419-0 [pii]
AID - 10.1016/j.immuni.2012.07.013 [doi]
PST - ppublish
SO  - Immunity. 2012 Oct 19;37(4):611-21. doi: 10.1016/j.immuni.2012.07.013. Epub 2012 
      Oct 11.