PMID- 22342873
OWN - NLM
STAT- MEDLINE
DCOM- 20120727
LR  - 20131121
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 73
IP  - 4
DP  - 2012 Apr
TI  - Evidence that HLA-DQ9 confers risk to celiac disease by presence of 
      DQ9-restricted gluten-specific T cells.
PG  - 376-81
LID - 10.1016/j.humimm.2012.01.016 [doi]
AB  - We describe the gluten T-cell response of a DR7DQ2/DR9DQ9 heterozygous celiac 
      disease patient (CD555). Interestingly, this patient had T cells recognizing 
      gluten in the context of human leukocyte antigen (HLA) molecules of both 
      haplotypes. For the DR9DQ9 haplotype, DQ9 was identified as the 
      antigen-presenting molecule. As DQ9 carries aspartate at DQ beta57 but is otherwise 
      identical to DQ8 and not considered associated with celiac disease, we aimed to 
      characterize this DQ9-restricted T-cell response in detail. By fractionation of 
      pepsin-trypsin digested gliadin we identified an epitope stimulatory for several 
      T-cell clones. This epitope was identical to an epitope (DQ8-glut-1) previously 
      identified in DQ8 patients. In CD555, this was the dominant DQ9-restricted 
      epitope, whereas no T-cell response was found toward two other DQ8-restricted 
      epitopes. These findings correlated with peptide binding data demonstrating that 
      this epitope bound better to DQ9 than the two other DQ8-restricted epitopes. 
      Although glutamine to glutamate exchange at P9 improved binding of all three 
      epitopes to DQ8, no such effect was observed for DQ9. The differential ability of 
      DQ8 and DQ9 to harness a negatively charged anchor at P9 may result in fewer 
      potential gluten epitopes in DQ9 patients. Our data further indicate that DQ9 is 
      a susceptibility factor for celiac disease.
CI  - Copyright (c) 2012 American Society for Histocompatibility and Immunogenetics. 
      Published by Elsevier Inc. All rights reserved.
FAU - Bodd, Michael
AU  - Bodd M
AD  - Centre for Immune Regulation and Department of Immunology, Oslo University 
      Hospital-Rikshospitalet, Oslo, Norway. michael.bodd@rr-research.no
FAU - Tollefsen, Stig
AU  - Tollefsen S
FAU - Bergseng, Elin
AU  - Bergseng E
FAU - Lundin, Knut E A
AU  - Lundin KE
FAU - Sollid, Ludvig M
AU  - Sollid LM
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120131
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (HLA-DQ9 antigen)
RN  - 0 (Peptides)
RN  - 0RH81L854J (Glutamine)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 8002-80-0 (Glutens)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigen Presentation/immunology
MH  - Celiac Disease/*genetics/*immunology
MH  - Epitopes, T-Lymphocyte/chemistry/*immunology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Glutamic Acid/metabolism
MH  - Glutamine/metabolism
MH  - Glutens/chemistry/*immunology
MH  - HLA-DQ Antigens/*genetics/*immunology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Peptides/chemistry/immunology
MH  - Protein Binding/immunology
MH  - Risk
MH  - T-Lymphocytes/*immunology
EDAT- 2012/02/22 06:00
MHDA- 2012/07/28 06:00
CRDT- 2012/02/21 06:00
PHST- 2011/11/02 00:00 [received]
PHST- 2012/01/06 00:00 [revised]
PHST- 2012/01/24 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/07/28 06:00 [medline]
AID - S0198-8859(12)00026-2 [pii]
AID - 10.1016/j.humimm.2012.01.016 [doi]
PST - ppublish
SO  - Hum Immunol. 2012 Apr;73(4):376-81. doi: 10.1016/j.humimm.2012.01.016. Epub 2012 
      Jan 31.