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Contents |
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278 a.a.
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100 a.a.
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197 a.a.
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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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Structure of a complex between the human natural killer cell receptor kir2dl2 and a class i mhc ligand hla-cw3
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Structure:
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Hla-cw3 (heavy chain). Chain: a. Fragment: extracellular alpha-1, alpha-2 and alpha-3 domains. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. Other_details: mature form. Peptide from importin alpha-2.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this peptide was chemically synthesized. The sequence is naturally found in homo sapiens (human)..
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Biol. unit:
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Tetramer (from
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Resolution:
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3.00Å
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R-factor:
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0.231
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R-free:
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0.294
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Authors:
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J.C.Boyington,S.A.Motyka,P.Schuck,A.G.Brooks,P.D.Sun
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Key ref:
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J.C.Boyington
et al.
(2000).
Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand.
Nature,
405,
537-543.
PubMed id:
DOI:
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Date:
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10-Feb-00
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Release date:
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14-Jun-00
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PROCHECK
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Headers
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References
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P10321
(1C07_HUMAN) -
HLA class I histocompatibility antigen, C alpha chain from Homo sapiens
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Seq:
Struc:
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366 a.a.
278 a.a.*
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DOI no:
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Nature
405:537-543
(2000)
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PubMed id:
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Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand.
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J.C.Boyington,
S.A.Motyka,
P.Schuck,
A.G.Brooks,
P.D.Sun.
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ABSTRACT
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Target cell lysis is regulated by natural killer (NK) cell receptors that
recognize class I MHC molecules. Here we report the crystal structure of the
human immunoglobulin-like NK cell receptor KIR2DL2 in complex with its class I
ligand HLA-Cw3 and peptide. KIR binds in a nearly orthogonal orientation across
the alpha1 and alpha2 helices of Cw3 and directly contacts positions 7 and 8 of
the peptide. No significant conformational changes in KIR occur on complex
formation. The receptor footprint on HLA overlaps with but is distinct from that
of the T-cell receptor. Charge complementarity dominates the KIR/HLA interface
and mutations that disrupt interface salt bridges substantially diminish
binding. Most contacts in the complex are between KIR and conserved HLA-C
residues, but a hydrogen bond between Lys 44 of KIR2DL2 and Asn 80 of Cw3
confers the allotype specificity. KIR contact requires position 8 of the peptide
to be a residue smaller than valine. A second KIR/HLA interface produced an
ordered receptor-ligand aggregation in the crystal which may resemble receptor
clustering during immune synapse formation.
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Selected figure(s)
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Figure 2.
Figure 2: The KIR2DL2/HLA-Cw3 interface. a, Charge
complementarity at the interface. Basic residues are dark blue,
acidic residues are red, and the remaining residues are coloured
by molecule. b,c, Stereo view of the interaction between domain
D1 of KIR, the GAV peptide and the  1
helix of HLA-Cw3 (b), and domain D2 of KIR, the hinge loop, the
GAV peptide and the 2
helix of HLA-Cw3 (c). KIR is shown in light blue, the GAV
peptide in purple and HLA-Cw3 in green. Selected hydrogen bonds
are represented by dotted lines.
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Figure 5.
Figure 5: KIR/HLA aggregation. The complex of KIR2DL2 and
HLA-Cw3 forms a regular oligomeric aggregate in the crystal
lattice. KIR and HLA-Cw3 are shown in green and orange,
respectively. The functional and oligomeric KIR/HLA-Cw3
interfaces are highlighted in pink and grey, respectively. The
predicted glycosylation sites (highlighted by blue dots) are at
residues 63, 157 and 190 for KIR, and at 86 for HLA-Cw3.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2000,
405,
537-543)
copyright 2000.
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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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G.Alter,
D.Heckerman,
A.Schneidewind,
L.Fadda,
C.M.Kadie,
J.M.Carlson,
C.Oniangue-Ndza,
M.Martin,
B.Li,
S.I.Khakoo,
M.Carrington,
T.M.Allen,
and
M.Altfeld
(2011).
HIV-1 adaptation to NK-cell-mediated immune pressure.
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Nature,
476,
96.
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J.P.Vivian,
R.C.Duncan,
R.Berry,
G.M.O'Connor,
H.H.Reid,
T.Beddoe,
S.Gras,
P.M.Saunders,
M.A.Olshina,
J.M.Widjaja,
C.M.Harpur,
J.Lin,
S.M.Maloveste,
D.A.Price,
B.A.Lafont,
D.W.McVicar,
C.S.Clements,
A.G.Brooks,
and
J.Rossjohn
(2011).
Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B.
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Nature,
479,
401-405.
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PDB code:
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K.S.Campbell,
and
A.K.Purdy
(2011).
Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations.
|
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Immunology,
132,
315-325.
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M.E.Blais,
T.Dong,
and
S.Rowland-Jones
(2011).
HLA-C as a mediator of natural killer and T-cell activation: spectator or key player?
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Immunology,
133,
1-7.
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|
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M.G.Joyce,
P.Tran,
M.A.Zhuravleva,
J.Jaw,
M.Colonna,
and
P.D.Sun
(2011).
Crystal structure of human natural cytotoxicity receptor NKp30 and identification of its ligand binding site.
|
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Proc Natl Acad Sci U S A,
108,
6223-6228.
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T.P.Abeyweera,
E.Merino,
and
M.Huse
(2011).
Inhibitory signaling blocks activating receptor clustering and induces cytoskeletal retraction in natural killer cells.
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J Cell Biol,
192,
675-690.
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Y.Li,
Q.Wang,
and
R.A.Mariuzza
(2011).
Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6.
|
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J Exp Med,
208,
703-714.
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L.Abi-Rached,
A.K.Moesta,
R.Rajalingam,
L.A.Guethlein,
and
P.Parham
(2010).
Human-specific evolution and adaptation led to major qualitative differences in the variable receptors of human and chimpanzee natural killer cells.
|
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PLoS Genet,
6,
e1001192.
|
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|
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L.Fadda,
G.Borhis,
P.Ahmed,
K.Cheent,
S.V.Pageon,
A.Cazaly,
S.Stathopoulos,
D.Middleton,
A.Mulder,
F.H.Claas,
T.Elliott,
D.M.Davis,
M.A.Purbhoo,
and
S.I.Khakoo
(2010).
Peptide antagonism as a mechanism for NK cell activation.
|
| |
Proc Natl Acad Sci U S A,
107,
10160-10165.
|
|
|
|
|
|
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N.G.Walpole,
L.Kjer-Nielsen,
L.Kostenko,
J.McCluskey,
A.G.Brooks,
J.Rossjohn,
and
C.S.Clements
(2010).
The structure and stability of the monomorphic HLA-G are influenced by the nature of the bound peptide.
|
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J Mol Biol,
397,
467-480.
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PDB codes:
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S.H.Hwang,
H.B.Oh,
S.E.Choi,
J.J.Seo,
J.H.Lee,
S.W.Cho,
J.M.Chae,
Y.S.Heo,
C.L.Chang,
and
E.Y.Lee
(2010).
Impact of amino acid substitution at residue 9 of HLA-A2 on the development of acute GVHD in Korean pediatric patients receiving unrelated hematopoietic stem cell transplantation.
|
| |
Transpl Int,
23,
1216-1222.
|
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|
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S.Rajagopalan,
and
E.O.Long
(2010).
Antagonizing inhibition gets NK cells going.
|
| |
Proc Natl Acad Sci U S A,
107,
10333-10334.
|
|
|
|
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|
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T.Gonen-Gross,
D.Goldman-Wohl,
B.Huppertz,
D.Lankry,
C.Greenfield,
S.Natanson-Yaron,
Y.Hamani,
R.Gilad,
S.Yagel,
and
O.Mandelboim
(2010).
Inhibitory NK receptor recognition of HLA-G: regulation by contact residues and by cell specific expression at the fetal-maternal interface.
|
| |
PLoS One,
5,
e8941.
|
|
|
|
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T.H.Brondijk,
T.de Ruiter,
J.Ballering,
H.Wienk,
R.J.Lebbink,
H.van Ingen,
R.Boelens,
R.W.Farndale,
L.Meyaard,
and
E.G.Huizinga
(2010).
Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI.
|
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Blood,
115,
1364-1373.
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PDB code:
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T.H.Nguyen,
L.C.Sullivan,
T.C.Kotsimbos,
A.P.Schwarer,
and
N.A.Mifsud
(2010).
Cross-presentation of HCMV chimeric protein enables generation and measurement of polyclonal T cells.
|
| |
Immunol Cell Biol,
88,
676-684.
|
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|
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|
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X.C.Li,
and
M.Raghavan
(2010).
Structure and function of major histocompatibility complex class I antigens.
|
| |
Curr Opin Organ Transplant,
15,
499-504.
|
|
|
|
|
|
|
C.Sola,
P.André,
C.Lemmers,
N.Fuseri,
C.Bonnafous,
M.Bléry,
N.R.Wagtmann,
F.Romagné,
E.Vivier,
and
S.Ugolini
(2009).
Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo.
|
| |
Proc Natl Acad Sci U S A,
106,
12879-12884.
|
|
|
|
|
|
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D.Sharma,
K.Bastard,
L.A.Guethlein,
P.J.Norman,
N.Yawata,
M.Yawata,
M.Pando,
H.Thananchai,
T.Dong,
S.Rowland-Jones,
F.M.Brodsky,
and
P.Parham
(2009).
Dimorphic motifs in D0 and D1+D2 domains of killer cell Ig-like receptor 3DL1 combine to form receptors with high, moderate, and no avidity for the complex of a peptide derived from HIV and HLA-A*2402.
|
| |
J Immunol,
183,
4569-4582.
|
|
|
|
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|
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J.Back,
E.L.Malchiodi,
S.Cho,
L.Scarpellino,
P.Schneider,
M.C.Kerzic,
R.A.Mariuzza,
and
W.Held
(2009).
Distinct conformations of Ly49 natural killer cell receptors mediate MHC class I recognition in trans and cis.
|
| |
Immunity,
31,
598-608.
|
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PDB codes:
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P.Kumar,
A.Vahedi-Faridi,
W.Saenger,
A.Ziegler,
and
B.Uchanska-Ziegler
(2009).
Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity.
|
| |
Protein Sci,
18,
37-49.
|
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PDB code:
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R.Bari,
T.Bell,
W.H.Leung,
Q.P.Vong,
W.K.Chan,
N.Das Gupta,
M.Holladay,
B.Rooney,
and
W.Leung
(2009).
Significant functional heterogeneity among KIR2DL1 alleles and a pivotal role of arginine 245.
|
| |
Blood,
114,
5182-5190.
|
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|
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T.Graef,
A.K.Moesta,
P.J.Norman,
L.Abi-Rached,
L.Vago,
A.M.Older Aguilar,
M.Gleimer,
J.A.Hammond,
L.A.Guethlein,
D.A.Bushnell,
P.J.Robinson,
and
P.Parham
(2009).
KIR2DS4 is a product of gene conversion with KIR3DL2 that introduced specificity for HLA-A*11 while diminishing avidity for HLA-C.
|
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J Exp Med,
206,
2557-2572.
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PDB code:
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Y.Chen,
Y.Shi,
H.Cheng,
Y.Q.An,
and
G.F.Gao
(2009).
Structural immunology and crystallography help immunologists see the immune system in action: how T and NK cells touch their ligands.
|
| |
IUBMB Life,
61,
579-590.
|
|
|
|
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|
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Y.Li,
M.Hofmann,
Q.Wang,
L.Teng,
L.K.Chlewicki,
H.Pircher,
and
R.A.Mariuzza
(2009).
Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.
|
| |
Immunity,
31,
35-46.
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PDB codes:
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B.A.Foley,
D.De Santis,
E.Van Beelen,
L.J.Lathbury,
F.T.Christiansen,
and
C.S.Witt
(2008).
The reactivity of Bw4+ HLA-B and HLA-A alleles with KIR3DL1: implications for patient and donor suitability for haploidentical stem cell transplantations.
|
| |
Blood,
112,
435-443.
|
|
|
|
|
|
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G.Minevich,
L.Kuhn,
C.Polistena,
J.Nuara,
and
R.Winchester
(2008).
Description of two new HLA-C alleles in a black South African population.
|
| |
Tissue Antigens,
71,
72-76.
|
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H.Achdout,
I.Manaster,
and
O.Mandelboim
(2008).
Influenza virus infection augments NK cell inhibition through reorganization of major histocompatibility complex class I proteins.
|
| |
J Virol,
82,
8030-8037.
|
|
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|
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J.Lu,
L.L.Marnell,
K.D.Marjon,
C.Mold,
T.W.Du Clos,
and
P.D.Sun
(2008).
Structural recognition and functional activation of FcgammaR by innate pentraxins.
|
| |
Nature,
456,
989-992.
|
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PDB code:
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L.Sibilio,
A.Martayan,
A.Setini,
E.Lo Monaco,
E.Tremante,
R.H.Butler,
and
P.Giacomini
(2008).
A single bottleneck in HLA-C assembly.
|
| |
J Biol Chem,
283,
1267-1274.
|
|
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|
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|
|
R.D.Levinson,
Z.Du,
L.Luo,
D.Monnet,
T.Tabary,
A.P.Brezin,
L.Zhao,
D.W.Gjertson,
G.N.Holland,
E.F.Reed,
J.H.Cohen,
and
R.Rajalingam
(2008).
Combination of KIR and HLA gene variants augments the risk of developing birdshot chorioretinopathy in HLA-A*29-positive individuals.
|
| |
Genes Immun,
9,
249-258.
|
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S.Kulkarni,
M.P.Martin,
and
M.Carrington
(2008).
The Yin and Yang of HLA and KIR in human disease.
|
| |
Semin Immunol,
20,
343-352.
|
|
|
|
|
|
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W.Held,
and
R.A.Mariuzza
(2008).
Cis interactions of immunoreceptors with MHC and non-MHC ligands.
|
| |
Nat Rev Immunol,
8,
269-278.
|
|
|
|
|
|
|
B.N.Savani,
S.Mielke,
S.Adams,
M.Uribe,
K.Rezvani,
A.S.Yong,
J.Zeilah,
R.Kurlander,
R.Srinivasan,
R.Childs,
N.Hensel,
and
A.J.Barrett
(2007).
Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia.
|
| |
Leukemia,
21,
2145-2152.
|
|
|
|
|
|
|
C.A.Velikovsky,
L.Deng,
L.K.Chlewicki,
M.M.Fernández,
V.Kumar,
and
R.A.Mariuzza
(2007).
Structure of natural killer receptor 2B4 bound to CD48 reveals basis for heterophilic recognition in signaling lymphocyte activation molecule family.
|
| |
Immunity,
27,
572-584.
|
|
|
PDB codes:
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D.Hatherley,
K.Harlos,
D.C.Dunlop,
D.I.Stuart,
and
A.N.Barclay
(2007).
The structure of the macrophage signal regulatory protein alpha (SIRPalpha) inhibitory receptor reveals a binding face reminiscent of that used by T cell receptors.
|
| |
J Biol Chem,
282,
14567-14575.
|
|
|
PDB code:
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|
|
|
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|
|
G.Yun,
J.Tolar,
A.K.Yerich,
S.G.Marsh,
J.Robinson,
H.Noreen,
B.R.Blazar,
and
J.S.Miller
(2007).
A novel method for KIR-ligand typing by pyrosequencing to predict NK cell alloreactivity.
|
| |
Clin Immunol,
123,
272-280.
|
|
|
|
|
|
|
L.C.Sullivan,
C.S.Clements,
T.Beddoe,
D.Johnson,
H.L.Hoare,
J.Lin,
T.Huyton,
E.J.Hopkins,
H.H.Reid,
M.C.Wilce,
J.Kabat,
F.Borrego,
J.E.Coligan,
J.Rossjohn,
and
A.G.Brooks
(2007).
The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition.
|
| |
Immunity,
27,
900-911.
|
|
|
PDB code:
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|
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|
|
|
|
|
L.Luo,
Z.Du,
S.K.Sharma,
R.Cullen,
S.Spellman,
E.F.Reed,
and
R.Rajalingam
(2007).
Chain-terminating natural mutations affect the function of activating KIR receptors 3DS1 and 2DS3.
|
| |
Immunogenetics,
59,
779-792.
|
|
|
|
|
|
|
M.D.Crew
(2007).
Play it in E or G: utilization of HLA-E and -G in xenotransplantation.
|
| |
Xenotransplantation,
14,
198-207.
|
|
|
|
|
|
|
P.J.Norman,
L.Abi-Rached,
K.Gendzekhadze,
D.Korbel,
M.Gleimer,
D.Rowley,
D.Bruno,
C.V.Carrington,
D.Chandanayingyong,
Y.H.Chang,
C.Crespí,
G.Saruhan-Direskeneli,
P.A.Fraser,
K.Hameed,
G.Kamkamidze,
K.A.Koram,
Z.Layrisse,
N.Matamoros,
J.Milà,
M.H.Park,
R.M.Pitchappan,
D.D.Ramdath,
M.Y.Shiau,
H.A.Stephens,
S.Struik,
D.H.Verity,
R.W.Vaughan,
D.Tyan,
R.W.Davis,
E.M.Riley,
M.Ronaghi,
and
P.Parham
(2007).
Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.
|
| |
Nat Genet,
39,
1092-1099.
|
|
|
|
|
|
|
Z.Du,
D.W.Gjertson,
E.F.Reed,
and
R.Rajalingam
(2007).
Receptor-ligand analyses define minimal killer cell Ig-like receptor (KIR) in humans.
|
| |
Immunogenetics,
59,
1.
|
|
|
|
|
|
|
A.A.Bashirova,
M.P.Martin,
D.W.McVicar,
and
M.Carrington
(2006).
The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense.
|
| |
Annu Rev Genomics Hum Genet,
7,
277-300.
|
|
|
|
|
|
|
A.Faik,
J.Abouzouhair,
and
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Tissue Antigens,
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PDB code:
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A.N.Barclay
(2003).
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PDB code:
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M.Shiroishi,
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J Exp Med,
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PDB code:
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A.Gilhar,
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Psoriasis is mediated by a cutaneous defect triggered by activated immunocytes: induction of psoriasis by cells with natural killer receptors.
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PDB code:
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and
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J Exp Med,
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PDB code:
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The functional binding site for the C-type lectin-like natural killer cell receptor Ly49A spans three domains of its major histocompatibility complex class I ligand.
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J Exp Med,
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Tissue Antigens,
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J Exp Med,
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PDB code:
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|
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|
|
|
|
|
E.J.Sundberg,
and
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J.Wang,
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Structural basis of cell-cell interactions in the immune system.
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Crystal structure and ligand binding properties of the D1D2 region of the inhibitory receptor LIR-1 (ILT2).
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| |
Immunity,
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|
|
PDB code:
|
|
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|
|
|
|
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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