PMID- 25452463
OWN - NLM
STAT- MEDLINE
DCOM- 20150313
LR  - 20220129
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 211
IP  - 13
DP  - 2014 Dec 15
TI  - The molecular bases of delta/alphabeta T cell-mediated antigen recognition.
PG  - 2599-615
LID - 10.1084/jem.20141764 [doi]
AB  - alphabeta and gammadelta T cells are disparate T cell lineages that can respond to distinct 
      antigens (Ags) via the use of the alphabeta and gammadelta T cell Ag receptors (TCRs), 
      respectively. Here we characterize a population of human T cells, which we term 
      delta/alphabeta T cells, expressing TCRs comprised of a TCR-delta variable gene (Vdelta1) fused to 
      joining alpha and constant alpha domains, paired with an array of TCR-beta chains. We 
      demonstrate that these cells, which represent  approximately 50% of all Vdelta1(+) human T cells, 
      can recognize peptide- and lipid-based Ags presented by human leukocyte antigen 
      (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, 
      CD1d-lipid Ag-reactive delta/alphabeta T cells recognized alpha-galactosylceramide (alpha-GalCer); 
      however, their fine specificity for other lipid Ags presented by CD1d, such as 
      alpha-glucosylceramide, was distinct from type I NKT cells. Thus, delta/alphabetaTCRs contribute 
      new patterns of Ag specificity to the human immune system. Furthermore, we 
      provide the molecular bases of how delta/alphabetaTCRs bind to their targets, with the 
      Vdelta1-encoded region providing a major contribution to delta/alphabetaTCR binding. Our 
      findings highlight how components from alphabeta and gammadeltaTCR gene loci can recombine to 
      confer Ag specificity, thus expanding our understanding of T cell biology and TCR 
      diversity.
CI  - (c) 2014 Pellicci et al.
FAU - Pellicci, Daniel G
AU  - Pellicci DG
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia 
      Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
FAU - Uldrich, Adam P
AU  - Uldrich AP
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia 
      Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
FAU - Le Nours, Jerome
AU  - Le Nours J
AD  - Department of Biochemistry and Molecular Biology, School of Biomedical Sciences 
      and Australian Research Council Centre of Excellence in Advanced Molecular 
      Imaging, Monash University, Clayton, Victoria 3800, Australia Department of 
      Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian 
      Research Council Centre of Excellence in Advanced Molecular Imaging, Monash 
      University, Clayton, Victoria 3800, Australia.
FAU - Ross, Fiona
AU  - Ross F
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia 
      Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
FAU - Chabrol, Eric
AU  - Chabrol E
AD  - Department of Biochemistry and Molecular Biology, School of Biomedical Sciences 
      and Australian Research Council Centre of Excellence in Advanced Molecular 
      Imaging, Monash University, Clayton, Victoria 3800, Australia.
FAU - Eckle, Sidonia B G
AU  - Eckle SB
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
FAU - de Boer, Renate
AU  - de Boer R
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, 
      Netherlands.
FAU - Lim, Ricky T
AU  - Lim RT
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
FAU - McPherson, Kirsty
AU  - McPherson K
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
FAU - Besra, Gurdyal
AU  - Besra G
AD  - School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, 
      England, UK.
FAU - Howell, Amy R
AU  - Howell AR
AD  - Department of Chemistry, University of Connecticut, Storrs, CT 06269.
FAU - Moretta, Lorenzo
AU  - Moretta L
AD  - Istituto Giannina Gaslini, 16147 Genova, Italy.
FAU - McCluskey, James
AU  - McCluskey J
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
FAU - Heemskerk, Mirjam H M
AU  - Heemskerk MH
AD  - Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, 
      Netherlands.
FAU - Gras, Stephanie
AU  - Gras S
AD  - Department of Biochemistry and Molecular Biology, School of Biomedical Sciences 
      and Australian Research Council Centre of Excellence in Advanced Molecular 
      Imaging, Monash University, Clayton, Victoria 3800, Australia Department of 
      Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian 
      Research Council Centre of Excellence in Advanced Molecular Imaging, Monash 
      University, Clayton, Victoria 3800, Australia.
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AD  - Department of Biochemistry and Molecular Biology, School of Biomedical Sciences 
      and Australian Research Council Centre of Excellence in Advanced Molecular 
      Imaging, Monash University, Clayton, Victoria 3800, Australia Department of 
      Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian 
      Research Council Centre of Excellence in Advanced Molecular Imaging, Monash 
      University, Clayton, Victoria 3800, Australia Institute of Infection and 
      Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, 
      Wales, UK jamie.rossjohn@monash.edu godfrey@unimelb.edu.au.
FAU - Godfrey, Dale I
AU  - Godfrey DI
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia 
      Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity and Australian Research Council Centre of Excellence in Advanced 
      Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia 
      jamie.rossjohn@monash.edu godfrey@unimelb.edu.au.
LA  - eng
SI  - PDB/1ZT4
SI  - PDB/2PO6
SI  - PDB/3LKN
SI  - PDB/4DZB
SI  - PDB/4LFH
SI  - PDB/4LHU
SI  - PDB/4QRR
SI  - PDB/4WNQ
SI  - PDB/4WO4
GR  - G1001750/MRC_/Medical Research Council/United Kingdom
GR  - R01 GM087136/GM/NIGMS NIH HHS/United States
GR  - R01 GM 087136/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141201
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Antigens, CD1d)
RN  - 0 (Galactosylceramides)
RN  - 0 (Lipids)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
RN  - 0 (alpha-galactosylceramide)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, CD1d/*immunology
MH  - Clone Cells
MH  - Galactosylceramides/immunology
MH  - Humans
MH  - Jurkat Cells
MH  - Lipids/immunology
MH  - Lymphocyte Activation/immunology
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Peptides/chemistry/immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/chemistry/*immunology
MH  - Receptors, Antigen, T-Cell, gamma-delta/chemistry/*immunology
MH  - T-Lymphocytes/*immunology
PMC - PMC4267242
EDAT- 2014/12/03 06:00
MHDA- 2015/03/17 06:00
PMCR- 2015/06/15
CRDT- 2014/12/03 06:00
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/03/17 06:00 [medline]
PHST- 2015/06/15 00:00 [pmc-release]
AID - jem.20141764 [pii]
AID - 20141764 [pii]
AID - 10.1084/jem.20141764 [doi]
PST - ppublish
SO  - J Exp Med. 2014 Dec 15;211(13):2599-615. doi: 10.1084/jem.20141764. Epub 2014 Dec 
      1.