PMID- 17629515
OWN - NLM
STAT- MEDLINE
DCOM- 20070828
LR  - 20070731
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 27
IP  - 1
DP  - 2007 Jul
TI  - A structural and immunological basis for the role of human leukocyte antigen DQ8 
      in celiac disease.
PG  - 23-34
AB  - The risk of celiac disease is strongly associated with human leukocyte antigen 
      (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of 
      HLA-DQ2-mediated celiac disease is established, the underlying basis for 
      HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) 
      responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted 
      and that multiple, mostly deamidated peptides derived from protease-sensitive 
      sites of gliadin were recognized. This pattern of reactivity contrasted with the 
      more absolute deamidation dependence and relative protease resistance of the 
      dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis 
      for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data 
      established that the molecular mechanisms underlying HLA-DQ8-mediated celiac 
      disease differed markedly from the HLA-DQ2-mediated form of the disease. 
      Accordingly, nondietary therapeutic interventions in celiac disease might need to 
      be tailored to the genotype of the individual.
FAU - Henderson, Kate N
AU  - Henderson KN
AD  - The Protein Crystallography Unit, Department of Biochemistry and Molecular 
      Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 
      3800, Australia.
FAU - Tye-Din, Jason A
AU  - Tye-Din JA
FAU - Reid, Hugh H
AU  - Reid HH
FAU - Chen, Zhenjun
AU  - Chen Z
FAU - Borg, Natalie A
AU  - Borg NA
FAU - Beissbarth, Tim
AU  - Beissbarth T
FAU - Tatham, Arthur
AU  - Tatham A
FAU - Mannering, Stuart I
AU  - Mannering SI
FAU - Purcell, Anthony W
AU  - Purcell AW
FAU - Dudek, Nadine L
AU  - Dudek NL
FAU - van Heel, David A
AU  - van Heel DA
FAU - McCluskey, James
AU  - McCluskey J
FAU - Rossjohn, Jamie
AU  - Rossjohn J
FAU - Anderson, Robert P
AU  - Anderson RP
LA  - eng
SI  - PDB/2NNA
GR  - gr068094ma/Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070712
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Amides)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (Peptide Fragments)
RN  - 9007-90-3 (Gliadin)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Amides/metabolism
MH  - Amino Acid Sequence
MH  - Antigen Presentation/immunology
MH  - Celiac Disease/*immunology/*metabolism
MH  - Cells, Cultured
MH  - Clone Cells
MH  - Crystallography, X-Ray
MH  - Gliadin/immunology/metabolism/ultrastructure
MH  - HLA-DQ Antigens/*chemistry/*physiology/ultrastructure
MH  - Humans
MH  - Hydrolysis
MH  - Molecular Sequence Data
MH  - Peptide Fragments/immunology/metabolism
MH  - Peptide Hydrolases/chemistry
MH  - Structure-Activity Relationship
MH  - Th1 Cells/immunology/metabolism
EDAT- 2007/07/17 09:00
MHDA- 2007/08/29 09:00
CRDT- 2007/07/17 09:00
PHST- 2006/08/29 00:00 [received]
PHST- 2007/04/17 00:00 [revised]
PHST- 2007/05/08 00:00 [accepted]
PHST- 2007/07/17 09:00 [pubmed]
PHST- 2007/08/29 09:00 [medline]
PHST- 2007/07/17 09:00 [entrez]
AID - S1074-7613(07)00327-5 [pii]
AID - 10.1016/j.immuni.2007.05.015 [doi]
PST - ppublish
SO  - Immunity. 2007 Jul;27(1):23-34. doi: 10.1016/j.immuni.2007.05.015. Epub 2007 Jul 
      12.