PMID- 21562577
OWN - NLM
STAT- MEDLINE
DCOM- 20120127
LR  - 20161125
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 12
IP  - 6
DP  - 2011 Sep
TI  - Functional consequences of HLA-DQ8 homozygosity versus heterozygosity for islet 
      autoimmunity in type 1 diabetes.
PG  - 415-27
LID - 10.1038/gene.2011.24 [doi]
AB  - Human leukocyte antigen (HLA) class II haplotypes are established risk factors in 
      type 1 diabetes (T1D). The heterozygous DQ2/8 genotype confers the highest risk, 
      whereas the DQ6/8 genotype is protective. We hypothesized that DQ2/8 
      trans-molecules composed of alpha and beta chains from DQ2 and DQ8 express unique beta-cell 
      epitopes, whereas DQ6 may interfere with peptide binding to DQ8. Here we show 
      that a single insulin epitope (InsB13-21) within the T1D prototype antigenic 
      InsB6-22 peptide can bind to both cis- and trans-dimers, although these molecules 
      display different peptide binding patterns. DQ6 binds a distinct insulin epitope 
      (InsB6-14). The phenotype of DQ8-restricted T cells from a T1D patient changed 
      from proinflammatory to anti-inflammatory in the presence of DQ6. Our data 
      provide new insights into both susceptible and protective mechanism of DQ, where 
      protecting HLA molecules bind autoantigens in a different (competing) binding 
      register leading to 'epitope stealing', thereby inducing a regulatory, rather 
      than a pathogenic immune response.
FAU - Eerligh, P
AU  - Eerligh P
AD  - Department of Immunohaematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - van Lummel, M
AU  - van Lummel M
FAU - Zaldumbide, A
AU  - Zaldumbide A
FAU - Moustakas, A K
AU  - Moustakas AK
FAU - Duinkerken, G
AU  - Duinkerken G
FAU - Bondinas, G
AU  - Bondinas G
FAU - Koeleman, B P C
AU  - Koeleman BP
FAU - Papadopoulos, G K
AU  - Papadopoulos GK
FAU - Roep, B O
AU  - Roep BO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110512
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Epitopes, B-Lymphocyte)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ2 antigen)
RN  - 0 (HLA-DQ6 antigen)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (Insulin)
RN  - 0 (Syndecans)
RN  - 549LM7U24W (thymosin beta(4))
RN  - 61512-21-8 (Thymosin)
SB  - IM
MH  - Adolescent
MH  - B-Lymphocytes/cytology/immunology
MH  - Diabetes Mellitus, Type 1/genetics/immunology/*metabolism
MH  - Epitopes, B-Lymphocyte/immunology
MH  - Genetic Predisposition to Disease
MH  - HLA-DQ Antigens/*genetics
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Insulin/genetics
MH  - Islets of Langerhans/*immunology
MH  - Male
MH  - Protein Binding
MH  - Syndecans/metabolism
MH  - T-Lymphocytes/cytology/immunology
MH  - Thymosin/metabolism
EDAT- 2011/05/13 06:00
MHDA- 2012/01/28 06:00
CRDT- 2011/05/13 06:00
PHST- 2011/05/13 06:00 [entrez]
PHST- 2011/05/13 06:00 [pubmed]
PHST- 2012/01/28 06:00 [medline]
AID - gene201124 [pii]
AID - 10.1038/gene.2011.24 [doi]
PST - ppublish
SO  - Genes Immun. 2011 Sep;12(6):415-27. doi: 10.1038/gene.2011.24. Epub 2011 May 12.