PMID- 22805744
OWN - NLM
STAT- MEDLINE
DCOM- 20130305
LR  - 20220129
IS  - 1462-3994 (Electronic)
IS  - 1462-3994 (Linking)
VI  - 14
DP  - 2012 Jul 6
TI  - On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A 
      molecules associated with celiac disease and type 1 diabetes.
PG  - e15
LID - 10.1017/erm.2012.9 [doi]
AB  - This review discusses mechanisms that link allelic variants of major 
      histocompatibility complex (MHC) class II molecules (MHCII) to immune pathology. 
      We focus on HLA (human leukocyte antigen)-DQ (DQ) alleles associated with celiac 
      disease (CD) and type 1 diabetes (T1D) and the role of the murine DQ-like allele, 
      H2-Ag7 (I-Ag7 or Ag7), in murine T1D. MHCII molecules bind peptides, and alleles 
      vary in their peptide-binding specificity. Disease-associated alleles permit 
      binding of disease-inducing peptides, such as gluten-derived, Glu-/Pro-rich 
      gliadin peptides in CD and peptides from islet autoantigens, including insulin, 
      in T1D. In addition, the CD-associated DQ2.5 and DQ8 alleles are unusual in their 
      interactions with factors that regulate their peptide loading, invariant chain 
      (Ii) and HLA-DM (DM). The same alleles, as well as other T1D DQ risk alleles (and 
      Ag7), share nonpolar residues in place of Asp at beta57 and prefer peptides that 
      place acidic side chains in a pocket in the MHCII groove (P9). Antigen-presenting 
      cells from T1D-susceptible mice and humans retain CLIP because of poor DM 
      editing, although underlying mechanisms differ between species. We propose that 
      these effects on peptide presentation make key contributions to CD and T1D 
      pathogenesis.
FAU - Busch, Robert
AU  - Busch R
AD  - Department of Medicine, University of Cambridge, Cambridge, UK. 
      rb468@medschl.cam.ac.uk
FAU - De Riva, Alessandra
AU  - De Riva A
FAU - Hadjinicolaou, Andreas V
AU  - Hadjinicolaou AV
FAU - Jiang, Wei
AU  - Jiang W
FAU - Hou, Tieying
AU  - Hou T
FAU - Mellins, Elizabeth D
AU  - Mellins ED
LA  - eng
GR  - F32 AI089080/AI/NIAID NIH HHS/United States
GR  - R21 DK079163/DK/NIDDK NIH HHS/United States
GR  - R01 AR061297/AR/NIAMS NIH HHS/United States
GR  - AI095813/AI/NIAID NIH HHS/United States
GR  - UL1 RR025744/RR/NCRR NIH HHS/United States
GR  - UL1 TR001085/TR/NCATS NIH HHS/United States
GR  - AR061297/AR/NIAMS NIH HHS/United States
GR  - 18543/ARC_/Arthritis Research UK/United Kingdom
GR  - R21 AI095813/AI/NIAID NIH HHS/United States
GR  - AI089080/AI/NIAID NIH HHS/United States
GR  - 18543/VAC_/Versus Arthritis/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120706
PL  - England
TA  - Expert Rev Mol Med
JT  - Expert reviews in molecular medicine
JID - 100939725
RN  - 0 (H-2 Antigens)
RN  - 0 (H-2A antigen)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (Peptides)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Celiac Disease/*genetics/immunology
MH  - Diabetes Mellitus, Type 1/*genetics/immunology
MH  - Genetic Variation/genetics
MH  - H-2 Antigens/*genetics/immunology
MH  - HLA-DQ Antigens/*genetics/immunology
MH  - Humans
MH  - Peptides/*genetics/immunology
PMC - PMC4157902
MID - NIHMS622870
EDAT- 2012/07/19 06:00
MHDA- 2013/03/06 06:00
PMCR- 2014/09/08
CRDT- 2012/07/19 06:00
PHST- 2012/07/19 06:00 [entrez]
PHST- 2012/07/19 06:00 [pubmed]
PHST- 2013/03/06 06:00 [medline]
PHST- 2014/09/08 00:00 [pmc-release]
AID - S1462399412000099 [pii]
AID - 10.1017/erm.2012.9 [doi]
PST - epublish
SO  - Expert Rev Mol Med. 2012 Jul 6;14:e15. doi: 10.1017/erm.2012.9.