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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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Crystal structure of a human vgamma9/vdelta2 t cell receptor
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Structure:
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Gamma-delta t-cell receptor. Chain: a, c, e, g. Synonym: t-cell receptor delta chain. Engineered: yes. Gamma-delta t-cell receptor. Chain: b, d, f, h. Synonym: t-cell receptor gamma chain. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: vd2, dd3, jd1, cd. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: vg9, jgp, cg1.
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Biol. unit:
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Dimer (from
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Resolution:
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3.12Å
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R-factor:
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0.219
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R-free:
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0.266
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Authors:
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T.J.Allison,C.C.Winter,J.J.Fournie,M.Bonneville,D.N.Garboczi
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Key ref:
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T.J.Allison
et al.
(2001).
Structure of a human gammadelta T-cell antigen receptor.
Nature,
411,
820-824.
PubMed id:
DOI:
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Date:
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16-Jan-01
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Release date:
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20-Jun-01
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PROCHECK
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Headers
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References
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DOI no:
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Nature
411:820-824
(2001)
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PubMed id:
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Structure of a human gammadelta T-cell antigen receptor.
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T.J.Allison,
C.C.Winter,
J.J.Fournié,
M.Bonneville,
D.N.Garboczi.
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ABSTRACT
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T-cell antigen receptors composed of gamma and delta polypeptide chains
(gammadelta TCRs) can directly recognize antigens in the form of intact proteins
or non-peptide compounds, unlike alphabeta TCRs, which recognize antigens bound
to major histocompatibility complex molecules (MHC). About 5% of peripheral
blood T cells bear gammadelta TCRs, most of which recognize non-peptide
phosphorylated antigens. Here we describe the 3.1 A resolution structure of a
human gammadelta TCR from a T-cell clone that is phosphoantigen-reactive. The
orientation of the variable (V) and constant (C) regions of the gammadelta TCR
is unique when compared with alphabeta TCRs or antibodies, and results from an
unusually small angle between the Vgamma and Cgamma domains. The
complementarity-determining regions (CDRs) of the V domains exhibit a chemically
reasonable binding site for phosphorylated antigens, providing a possible
explanation for the canonical usage of the Vgamma9 and Vdelta2 gene segments by
phosphoantigen-reactive receptors. Although the gammadelta TCR V domains are
similar in overall structure to those of alphabeta TCRs, gammadelta TCR C
domains are markedly different. Structural differences in Cgamma and Cdelta, and
in the location of the disulphide bond between them, may enable gammadelta TCRs
to form different recognition/signalling complexes than alphabeta TCRs.
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Selected figure(s)
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Figure 1.
Figure 1: Views of the G115 V bold gamma- 9V
delta- 2
TCR. a, View of V  and
C (red)
and V  and
C (gold)
domains. CDR loops are at the top. b, View after a 90° rotation
around the vertical axis. The nine  -strands
of the V domains are labelled A -G, including A', C', and C".
The seven -strands
of the C domains are labelled A -G. In each domain, strands A,
B, E, and D form one -sheet,
and strands G, F and C (including A', C' and C" in the V
domains) form the other sheet. The V -V
interface
involves the A'GFCC'C" -sheets.
The C -C
[139]delta interface involves the ABED [140]beta -sheets.
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Figure 3.
Figure 3: Surface representations of G115. a, The surface of
G115 is coloured by CDR loops (CDR1, blue; CDR2, green; HV4,
pink; and CDR3, red). b, 3-formyl-1-butyl-pyrophosphate is shown
as a drawing and as a space-filling model (at the same scale as
G115 in a and c). c, The surface potential of G115 is
colour-coded from red (-10 kT) to blue (+10 kT). The top of the
molecule, containing the CDR loops, is facing the viewer. The
cleft between the two CDR3 loops contains positively charged
patches (blue), which line the phosphoantigen-binding site. d,
Enlarged view of the cleft shows the location of charged
(negative in red; positive in blue), hydrophobic (yellow) and
polar (green) residues.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2001,
411,
820-824)
copyright 2001.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
|
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Reference
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B.Xu,
J.C.Pizarro,
M.A.Holmes,
C.McBeth,
V.Groh,
T.Spies,
and
R.K.Strong
(2011).
Crystal structure of a gammadelta T-cell receptor specific for the human MHC class I homolog MICA.
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Proc Natl Acad Sci U S A,
108,
2414-2419.
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PDB code:
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E.Champagne
(2011).
γδ T cell Receptor Ligands and Modes of Antigen Recognition.
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Arch Immunol Ther Exp (Warsz),
59,
117-137.
|
|
|
|
|
|
|
E.M.Urban,
A.I.Chapoval,
and
C.D.Pauza
(2010).
Repertoire development and the control of cytotoxic/effector function in human gammadelta T cells.
|
| |
Clin Dev Immunol,
2010,
732893.
|
|
|
|
|
|
|
G.I.van Boxel,
S.Holmes,
L.Fugger,
and
E.Y.Jones
(2010).
An alternative conformation of the T-cell receptor alpha constant region.
|
| |
J Mol Biol,
400,
828-837.
|
|
|
PDB code:
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|
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|
|
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S.S.Pang,
R.Berry,
Z.Chen,
L.Kjer-Nielsen,
M.A.Perugini,
G.F.King,
C.Wang,
S.H.Chew,
N.L.La Gruta,
N.K.Williams,
T.Beddoe,
T.Tiganis,
N.P.Cowieson,
D.I.Godfrey,
A.W.Purcell,
M.C.Wilce,
J.McCluskey,
and
J.Rossjohn
(2010).
The structural basis for autonomous dimerization of the pre-T-cell antigen receptor.
|
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Nature,
467,
844-848.
|
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PDB code:
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E.M.Urban,
H.Li,
C.Armstrong,
C.Focaccetti,
C.Cairo,
and
C.D.Pauza
(2009).
Control of CD56 expression and tumor cell cytotoxicity in human Vgamma2Vdelta2 T cells.
|
| |
BMC Immunol,
10,
50.
|
|
|
|
|
|
|
L.Boucontet,
M.Grana,
P.M.Alzari,
and
P.Pereira
(2009).
Mechanisms determining cell membrane expression of different gammadelta TCR chain pairings.
|
| |
Eur J Immunol,
39,
1937-1946.
|
|
|
|
|
|
|
M.Eberl,
G.W.Roberts,
S.Meuter,
J.D.Williams,
N.Topley,
and
B.Moser
(2009).
A rapid crosstalk of human gammadelta T cells and monocytes drives the acute inflammation in bacterial infections.
|
| |
PLoS Pathog,
5,
e1000308.
|
|
|
|
|
|
|
W.K.Born,
and
R.L.O'Brien
(2009).
Antigen-restricted gammadelta T-cell receptors?
|
| |
Arch Immunol Ther Exp (Warsz),
57,
129-135.
|
|
|
|
|
|
|
C.T.Spencer,
G.Abate,
A.Blazevic,
and
D.F.Hoft
(2008).
Only a subset of phosphoantigen-responsive gamma9delta2 T cells mediate protective tuberculosis immunity.
|
| |
J Immunol,
181,
4471-4484.
|
|
|
|
|
|
|
E.J.Adams,
P.Strop,
S.Shin,
Y.H.Chien,
and
K.C.Garcia
(2008).
An autonomous CDR3delta is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by gammadelta T cells.
|
| |
Nat Immunol,
9,
777-784.
|
|
|
|
|
|
|
G.Sarikonda,
H.Wang,
K.J.Puan,
X.H.Liu,
H.K.Lee,
Y.Song,
M.D.Distefano,
E.Oldfield,
G.D.Prestwich,
and
C.T.Morita
(2008).
Photoaffinity antigens for human gammadelta T cells.
|
| |
J Immunol,
181,
7738-7750.
|
|
|
|
|
|
|
H.Chen,
X.He,
Z.Wang,
D.Wu,
H.Zhang,
C.Xu,
H.He,
L.Cui,
D.Ba,
and
W.He
(2008).
Identification of human T cell receptor gammadelta-recognized epitopes/proteins via CDR3delta peptide-based immunobiochemical strategy.
|
| |
J Biol Chem,
283,
12528-12537.
|
|
|
|
|
|
|
H.Wei,
D.Huang,
X.Lai,
M.Chen,
W.Zhong,
R.Wang,
and
Z.W.Chen
(2008).
Definition of APC presentation of phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate to Vgamma2Vdelta 2 TCR.
|
| |
J Immunol,
181,
4798-4806.
|
|
|
|
|
|
|
B.Moser,
and
M.Eberl
(2007).
gammadelta T cells: novel initiators of adaptive immunity.
|
| |
Immunol Rev,
215,
89.
|
|
|
|
|
|
|
C.T.Morita,
C.Jin,
G.Sarikonda,
and
H.Wang
(2007).
Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens.
|
| |
Immunol Rev,
215,
59-76.
|
|
|
|
|
|
|
R.L.O'Brien,
C.L.Roark,
N.Jin,
M.K.Aydintug,
J.D.French,
J.L.Chain,
J.M.Wands,
M.Johnston,
and
W.K.Born
(2007).
gammadelta T-cell receptors: functional correlations.
|
| |
Immunol Rev,
215,
77-88.
|
|
|
|
|
|
|
S.Beetz,
L.Marischen,
D.Kabelitz,
and
D.Wesch
(2007).
Human gamma delta T cells: candidates for the development of immunotherapeutic strategies.
|
| |
Immunol Res,
37,
97.
|
|
|
|
|
|
|
W.K.Born,
N.Jin,
M.K.Aydintug,
J.M.Wands,
J.D.French,
C.L.Roark,
and
R.L.O'Brien
(2007).
gammadelta T lymphocytes-selectable cells within the innate system?
|
| |
J Clin Immunol,
27,
133-144.
|
|
|
|
|
|
|
E.Untersmayr,
and
E.Jensen-Jarolim
(2006).
Mechanisms of type I food allergy.
|
| |
Pharmacol Ther,
112,
787-798.
|
|
|
|
|
|
|
I.Tikhonov,
C.O.Deetz,
R.Paca,
S.Berg,
V.Lukyanenko,
J.K.Lim,
and
C.D.Pauza
(2006).
Human Vgamma2Vdelta2 T cells contain cytoplasmic RANTES.
|
| |
Int Immunol,
18,
1243-1251.
|
|
|
|
|
|
|
J.P.Lauritsen,
M.C.Haks,
J.M.Lefebvre,
D.J.Kappes,
and
D.L.Wiest
(2006).
Recent insights into the signals that control alphabeta/gammadelta-lineage fate.
|
| |
Immunol Rev,
209,
176-190.
|
|
|
|
|
|
|
M.F.Criscitiello,
M.Saltis,
and
M.F.Flajnik
(2006).
An evolutionarily mobile antigen receptor variable region gene: doubly rearranging NAR-TcR genes in sharks.
|
| |
Proc Natl Acad Sci U S A,
103,
5036-5041.
|
|
|
|
|
|
|
M.G.Rudolph,
R.L.Stanfield,
and
I.A.Wilson
(2006).
How TCRs bind MHCs, peptides, and coreceptors.
|
| |
Annu Rev Immunol,
24,
419-466.
|
|
|
|
|
|
|
T.P.Baum,
V.Hierle,
N.Pasqual,
F.Bellahcene,
D.Chaume,
M.P.Lefranc,
E.Jouvin-Marche,
P.N.Marche,
and
J.Demongeot
(2006).
IMGT/GeneInfo: T cell receptor gamma TRG and delta TRD genes in database give access to all TR potential V(D)J recombinations.
|
| |
BMC Bioinformatics,
7,
224.
|
|
|
|
|
|
|
Y.Tanaka
(2006).
Human gamma delta T cells and tumor immunotherapy.
|
| |
J Clin Exp Hematop,
46,
11-23.
|
|
|
|
|
|
|
A.Sturm,
K.Rilling,
D.C.Baumgart,
K.Gargas,
T.Abou-Ghazalé,
B.Raupach,
J.Eckert,
R.R.Schumann,
C.Enders,
U.Sonnenborn,
B.Wiedenmann,
and
A.U.Dignass
(2005).
Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling.
|
| |
Infect Immun,
73,
1452-1465.
|
|
|
|
|
|
|
C.Cairo,
N.Propp,
A.M.Hebbeler,
V.Colizzi,
and
C.D.Pauza
(2005).
The Vgamma2/Vdelta2 T-cell repertoire in Macaca fascicularis: functional responses to phosphoantigen stimulation by the Vgamma2/Jgamma1.2 subset.
|
| |
Immunology,
115,
197-205.
|
|
|
|
|
|
|
D.N.Garboczi
(2005).
Structural biology. "D" is not for diversity.
|
| |
Science,
308,
209-210.
|
|
|
|
|
|
|
E.J.Adams,
Y.H.Chien,
and
K.C.Garcia
(2005).
Structure of a gammadelta T cell receptor in complex with the nonclassical MHC T22.
|
| |
Science,
308,
227-231.
|
|
|
PDB code:
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E.Scotet,
L.O.Martinez,
E.Grant,
R.Barbaras,
P.Jenö,
M.Guiraud,
B.Monsarrat,
X.Saulquin,
S.Maillet,
J.P.Estève,
F.Lopez,
B.Perret,
X.Collet,
M.Bonneville,
and
E.Champagne
(2005).
Tumor recognition following Vgamma9Vdelta2 T cell receptor interactions with a surface F1-ATPase-related structure and apolipoprotein A-I.
|
| |
Immunity,
22,
71-80.
|
|
|
|
|
|
|
E.Viey,
C.Laplace,
and
B.Escudier
(2005).
Peripheral gammadelta T-lymphocytes as an innovative tool in immunotherapy for metastatic renal cell carcinoma.
|
| |
Expert Rev Anticancer Ther,
5,
973-986.
|
|
|
|
|
|
|
R.Antonacci,
C.Lanave,
L.Del Faro,
G.Vaccarelli,
S.Ciccarese,
and
S.Massari
(2005).
Artiodactyl emergence is accompanied by the birth of an extensive pool of diverse germline TRDV1 genes.
|
| |
Immunogenetics,
57,
254-266.
|
|
|
|
|
|
|
V.Kunzmann,
and
M.Wilhelm
(2005).
Anti-lymphoma effect of gammadelta T cells.
|
| |
Leuk Lymphoma,
46,
671-680.
|
|
|
|
|
|
|
H.Nishimura,
M.Hirokawa,
N.Fujishima,
M.Fujishima,
I.Miura,
and
K.Sawada
(2004).
Contribution of complementarity-determining region 3 of the T-cell receptor Vdelta2 chain to the recognition of aminobisphosphonates by human gammadelta T-cells.
|
| |
Int J Hematol,
79,
369-376.
|
|
|
|
|
|
|
J.E.Gumperz
(2004).
Antigen specificity of semi-invariant CD1d-restricted T cell receptors: the best of both worlds?
|
| |
Immunol Cell Biol,
82,
285-294.
|
|
|
|
|
|
|
K.L.Arnett,
S.C.Harrison,
and
D.C.Wiley
(2004).
Crystal structure of a human CD3-epsilon/delta dimer in complex with a UCHT1 single-chain antibody fragment.
|
| |
Proc Natl Acad Sci U S A,
101,
16268-16273.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Z.Y.Sun,
S.T.Kim,
I.C.Kim,
A.Fahmy,
E.L.Reinherz,
and
G.Wagner
(2004).
Solution structure of the CD3epsilondelta ectodomain and comparison with CD3epsilongamma as a basis for modeling T cell receptor topology and signaling.
|
| |
Proc Natl Acad Sci U S A,
101,
16867-16872.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
B.Malissen
(2003).
An evolutionary and structural perspective on T cell antigen receptor function.
|
| |
Immunol Rev,
191,
7.
|
|
|
|
|
|
|
C.Breithaupt,
A.Schubart,
H.Zander,
A.Skerra,
R.Huber,
C.Linington,
and
U.Jacob
(2003).
Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein.
|
| |
Proc Natl Acad Sci U S A,
100,
9446-9451.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
J.E.Guerrero,
D.P.Pacheco,
C.F.Suárez,
P.Martínez,
F.Aristizabal,
C.A.Moncada,
M.E.Patarroyo,
and
M.A.Patarroyo
(2003).
Characterizing T-cell receptor gamma-variable gene in Aotus nancymaae owl monkey peripheral blood.
|
| |
Tissue Antigens,
62,
472-482.
|
|
|
|
|
|
|
L.Kjer-Nielsen,
C.S.Clements,
A.W.Purcell,
A.G.Brooks,
J.C.Whisstock,
S.R.Burrows,
J.McCluskey,
and
J.Rossjohn
(2003).
A structural basis for the selection of dominant alphabeta T cell receptors in antiviral immunity.
|
| |
Immunity,
18,
53-64.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
L.Kjer-Nielsen,
C.S.Clements,
A.G.Brooks,
A.W.Purcell,
J.McCluskey,
and
J.Rossjohn
(2002).
The 1.5 A crystal structure of a highly selected antiviral T cell receptor provides evidence for a structural basis of immunodominance.
|
| |
Structure,
10,
1521-1532.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.Aljurf,
A.Ezzat,
and
M.O Musa
(2002).
Emerging role of gammadelta T-cells in health and disease.
|
| |
Blood Rev,
16,
203-206.
|
|
|
|
|
|
|
M.Eberl,
B.Altincicek,
A.K.Kollas,
S.Sanderbrand,
U.Bahr,
A.Reichenberg,
E.Beck,
D.Foster,
J.Wiesner,
M.Hintz,
and
H.Jomaa
(2002).
Accumulation of a potent gammadelta T-cell stimulator after deletion of the lytB gene in Escherichia coli.
|
| |
Immunology,
106,
200-211.
|
|
|
|
|
|
|
M.G.Rudolph,
and
I.A.Wilson
(2002).
The specificity of TCR/pMHC interaction.
|
| |
Curr Opin Immunol,
14,
52-65.
|
|
|
|
|
|
|
M.G.Rudolph,
J.G.Luz,
and
I.A.Wilson
(2002).
Structural and thermodynamic correlates of T cell signaling.
|
| |
Annu Rev Biophys Biomol Struct,
31,
121-149.
|
|
|
|
|
|
|
R.E.Rojas,
M.Torres,
J.J.Fournié,
C.V.Harding,
and
W.H.Boom
(2002).
Phosphoantigen presentation by macrophages to mycobacterium tuberculosis--reactive Vgamma9Vdelta2+ T cells: modulation by chloroquine.
|
| |
Infect Immun,
70,
4019-4027.
|
|
|
|
|
|
|
S.M.Hayes,
and
P.E.Love
(2002).
Distinct structure and signaling potential of the gamma delta TCR complex.
|
| |
Immunity,
16,
827-838.
|
|
|
|
|
|
|
S.R.Carding,
and
P.J.Egan
(2002).
Gammadelta T cells: functional plasticity and heterogeneity.
|
| |
Nat Rev Immunol,
2,
336-345.
|
|
|
|
|
|
|
A.Bendelac,
M.Bonneville,
and
J.F.Kearney
(2001).
Autoreactivity by design: innate B and T lymphocytes.
|
| |
Nat Rev Immunol,
1,
177-186.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
