PMID- 24777060
OWN - NLM
STAT- MEDLINE
DCOM- 20140718
LR  - 20211021
IS  - 1545-9985 (Electronic)
IS  - 1545-9985 (Linking)
VI  - 21
IP  - 5
DP  - 2014 May
TI  - T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac 
      disease.
PG  - 480-8
LID - 10.1038/nsmb.2817 [doi]
AB  - 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-alpha1a and DQ2.5-glia-alpha2. We determined 
      the ternary structures of four distinct biased TCRs specific for those epitopes. 
      All three TCRs specific for DQ2.5-glia-alpha2 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 CDR3beta loop 
      acted as the lynchpin within this common docking footprint. Although the TCRs 
      specific for DQ2.5-glia-alpha1a and DQ2.5-glia-alpha2 docked similarly, their 
      interactions with the respective gliadin determinants differed markedly, thereby 
      providing a basis for epitope specificity.
FAU - Petersen, Jan
AU  - Petersen J
AD  - 1] Department of Biochemistry and Molecular Biology, School of Biomedical 
      Sciences, Monash University, Clayton, Victoria, Australia. [2].
FAU - Montserrat, Veronica
AU  - Montserrat V
AD  - 1] Department of Immunohematology and Blood Transfusion, Leiden University 
      Medical Center, Leiden, The Netherlands. [2].
FAU - Mujico, Jorge R
AU  - Mujico JR
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - Loh, Khai Lee
AU  - Loh KL
AD  - Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, 
      Monash University, Clayton, Victoria, Australia.
FAU - Beringer, Dennis X
AU  - Beringer DX
AD  - Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, 
      Monash University, Clayton, Victoria, Australia.
FAU - van Lummel, Menno
AU  - van Lummel M
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - Thompson, Allan
AU  - Thompson A
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - Mearin, M Luisa
AU  - Mearin ML
AD  - Department of Pediatrics, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Schweizer, Joachim
AU  - Schweizer J
AD  - Department of Pediatrics, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Kooy-Winkelaar, Yvonne
AU  - Kooy-Winkelaar Y
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - van Bergen, Jeroen
AU  - van Bergen J
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - Drijfhout, Jan W
AU  - Drijfhout JW
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - Kan, Wan-Ting
AU  - Kan WT
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity, University of Melbourne, Parkville, Victoria, Australia.
FAU - La Gruta, Nicole L
AU  - La Gruta NL
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity, University of Melbourne, Parkville, Victoria, Australia.
FAU - Anderson, Robert P
AU  - Anderson RP
AD  - ImmusanT, Inc., Cambridge, Massachusetts, USA.
FAU - Reid, Hugh H
AU  - Reid HH
AD  - 1] Department of Biochemistry and Molecular Biology, School of Biomedical 
      Sciences, Monash University, Clayton, Victoria, Australia. [2] [3].
FAU - Koning, Frits
AU  - Koning F
AD  - 1] Department of Immunohematology and Blood Transfusion, Leiden University 
      Medical Center, Leiden, The Netherlands. [2] [3].
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AD  - 1] Department of Biochemistry and Molecular Biology, School of Biomedical 
      Sciences, Monash University, Clayton, Victoria, Australia. [2] Institute of 
      Infection and Immunity, Cardiff University School of Medicine, Heath Park, 
      Cardiff, UK. [3] Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, Monash University, Clayton, Victoria, Australia. [4] [5].
LA  - eng
SI  - PDB/4OZF
SI  - PDB/4OZG
SI  - PDB/4OZH
SI  - PDB/4OZI
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140428
PL  - United States
TA  - Nat Struct Mol Biol
JT  - Nature structural & molecular biology
JID - 101186374
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 9007-90-3 (Gliadin)
SB  - IM
CIN - Nat Struct Mol Biol. 2014 May;21(5):429-31. PMID: 24777059
MH  - Celiac Disease/*immunology
MH  - Epitopes, T-Lymphocyte/*chemistry
MH  - Gliadin/*chemistry/immunology
MH  - HLA-DQ Antigens/*chemistry
MH  - Humans
MH  - Immunogenetic Phenomena
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Receptors, Antigen, T-Cell/*chemistry
MH  - Triticum
EDAT- 2014/04/30 06:00
MHDA- 2014/07/19 06:00
CRDT- 2014/04/30 06:00
PHST- 2014/02/12 00:00 [received]
PHST- 2014/03/28 00:00 [accepted]
PHST- 2014/04/30 06:00 [entrez]
PHST- 2014/04/30 06:00 [pubmed]
PHST- 2014/07/19 06:00 [medline]
AID - nsmb.2817 [pii]
AID - 10.1038/nsmb.2817 [doi]
PST - ppublish
SO  - Nat Struct Mol Biol. 2014 May;21(5):480-8. doi: 10.1038/nsmb.2817. Epub 2014 Apr 
      28.