PMID- 26838051
OWN - NLM
STAT- MEDLINE
DCOM- 20171107
LR  - 20230203
IS  - 1935-3456 (Electronic)
IS  - 1933-0219 (Linking)
VI  - 9
IP  - 3
DP  - 2016 May
TI  - TCR sequencing of single cells reactive to DQ2.5-glia-alpha2 and DQ2.5-glia-omega2 
      reveals clonal expansion and epitope-specific V-gene usage.
PG  - 587-96
LID - 10.1038/mi.2015.147 [doi]
AB  - CD4+ T cells recognizing dietary gluten epitopes in the context of 
      disease-associated human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 molecules are the 
      key players in celiac disease pathogenesis. Here, we conducted a large-scale 
      single-cell paired T-cell receptor (TCR) sequencing study to characterize the TCR 
      repertoire for two homologous immunodominant gluten epitopes, DQ2.5-glia-alpha2 and 
      DQ2.5-glia-omega2, in blood of celiac disease patients after oral gluten challenge. 
      Despite sequence similarity of the epitopes, the TCR repertoires are unique but 
      shared several overall features. We demonstrate that clonally expanded T cells 
      dominate the T-cell responses to both epitopes. Moreover, we find V-gene bias of 
      TRAV26, TRAV4, and TRBV7 in DQ2.5-glia-alpha2 reactive TCRs, while DQ2.5-glia-omega2 TCRs 
      displayed significant bias toward TRAV4 and TRBV4. The knowledge that 
      antigen-specific TCR repertoire in chronic inflammatory diseases tends to be 
      dominated by a few expanded clones that use the same TCR V-gene segments across 
      patients is important information for HLA-associated diseases where the antigen 
      is unknown.
FAU - Dahal-Koirala, S
AU  - Dahal-Koirala S
AD  - Centre for Immune Regulation, Department of Immunology, University of Oslo and 
      Oslo University Hospital-Rikshospitalet, Oslo, Norway.
FAU - Risnes, L F
AU  - Risnes LF
AD  - Centre for Immune Regulation, Department of Immunology, University of Oslo and 
      Oslo University Hospital-Rikshospitalet, Oslo, Norway.
FAU - Christophersen, A
AU  - Christophersen A
AD  - Centre for Immune Regulation, Department of Immunology, University of Oslo and 
      Oslo University Hospital-Rikshospitalet, Oslo, Norway.
FAU - Sarna, V K
AU  - Sarna VK
AD  - Centre for Immune Regulation, Department of Immunology, University of Oslo and 
      Oslo University Hospital-Rikshospitalet, Oslo, Norway.
FAU - Lundin, K Ea
AU  - Lundin KE
AD  - Centre for Immune Regulation, Department of Immunology, University of Oslo and 
      Oslo University Hospital-Rikshospitalet, Oslo, Norway.
AD  - Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, Oslo, 
      Norway.
FAU - Sollid, L M
AU  - Sollid LM
AD  - Centre for Immune Regulation, Department of Immunology, University of Oslo and 
      Oslo University Hospital-Rikshospitalet, Oslo, Norway.
FAU - Qiao, S W
AU  - Qiao SW
AD  - Centre for Immune Regulation, Department of Immunology, University of Oslo and 
      Oslo University Hospital-Rikshospitalet, Oslo, Norway.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160203
PL  - United States
TA  - Mucosal Immunol
JT  - Mucosal immunology
JID - 101299742
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ2 antigen)
RN  - 0 (HLA-DQ8 antigen)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 8002-80-0 (Glutens)
RN  - 9007-49-2 (DNA)
SB  - IM
CIN - Mucosal Immunol. 2016 May;9(3):583-6. PMID: 27007675
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Celiac Disease/*immunology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Clonal Selection, Antigen-Mediated
MH  - DNA/*analysis
MH  - Glutens/immunology
MH  - HLA-DQ Antigens/metabolism
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immunodominant Epitopes/immunology
MH  - Lymphocyte Activation
MH  - Receptors, Antigen, T-Cell/*genetics
MH  - Single-Cell Analysis
EDAT- 2016/02/04 06:00
MHDA- 2017/11/08 06:00
CRDT- 2016/02/04 06:00
PHST- 2015/09/16 00:00 [received]
PHST- 2015/11/29 00:00 [accepted]
PHST- 2016/02/04 06:00 [entrez]
PHST- 2016/02/04 06:00 [pubmed]
PHST- 2017/11/08 06:00 [medline]
AID - S1933-0219(22)00887-X [pii]
AID - 10.1038/mi.2015.147 [doi]
PST - ppublish
SO  - Mucosal Immunol. 2016 May;9(3):587-96. doi: 10.1038/mi.2015.147. Epub 2016 Feb 3.