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268 a.a.
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100 a.a.
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199 a.a.
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240 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 the hla-e-vmaprtlil/kk50.4 tcr complex
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Structure:
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Hla class i histocompatibility antigen, alpha chain e. Chain: a. Fragment: extracellular domain. Synonym: hla-e 103, Mhc class i antigen e. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. Vmaprtlil peptide from cmv gpul40.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: de novo peptide synthesis.
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Biol. unit:
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Pentamer (from
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Resolution:
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2.60Å
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R-factor:
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0.218
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R-free:
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0.292
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Authors:
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H.L.Hoare,J.Rossjohn
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Key ref:
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H.L.Hoare
et al.
(2006).
Structural basis for a major histocompatibility complex class Ib-restricted T cell response.
Nat Immunol,
7,
256-264.
PubMed id:
DOI:
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Date:
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27-Oct-05
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Release date:
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21-Mar-06
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PROCHECK
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Headers
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References
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P13747
(HLAE_HUMAN) -
HLA class I histocompatibility antigen, alpha chain E from Homo sapiens
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Seq:
Struc:
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358 a.a.
268 a.a.*
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P61769
(B2MG_HUMAN) -
Beta-2-microglobulin from Homo sapiens
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Seq:
Struc:
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119 a.a.
100 a.a.*
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DOI no:
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Nat Immunol
7:256-264
(2006)
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PubMed id:
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Structural basis for a major histocompatibility complex class Ib-restricted T cell response.
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H.L.Hoare,
L.C.Sullivan,
G.Pietra,
C.S.Clements,
E.J.Lee,
L.K.Ely,
T.Beddoe,
M.Falco,
L.Kjer-Nielsen,
H.H.Reid,
J.McCluskey,
L.Moretta,
J.Rossjohn,
A.G.Brooks.
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ABSTRACT
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In contrast to antigen-specific immunity orchestrated by major
histocompatibility complex (MHC) class Ia molecules, the ancestrally related
nonclassical MHC class Ib molecules generally mediate innate immune responses.
Here we have demonstrated the structural basis by which the MHC class Ib
molecule HLA-E mediates an adaptive MHC-restricted cytotoxic T lymphocyte
response to human cytomegalovirus. Highly constrained by host genetics, the
response showed notable fine specificity for position 8 of the viral peptide,
which is the sole discriminator of self versus nonself. Despite the evolutionary
divergence of MHC class Ia and class Ib molecules, the structure of the T cell
receptor-MHC class Ib complex was very similar to that of conventional T cell
receptor-MHC class Ia complexes. These results emphasize the evolutionary
'ambiguity' of HLA-E, which not only interacts with innate immune receptors but
also has the functional capacity to mediate virus-specific cytotoxic T
lymphocyte responses during adaptive immunity.
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Selected figure(s)
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Figure 4.
Figure 4. Contribution of CDRs to the 'footprint' of the KK50.4
TCR on HLA-E-(VMAPRTLIL). The 'footprint' of the KK50.4 TCR
on HLA-E-(VMAPRTLIL) (a) is compared with 'footprint' of the
LC13 TCR on HLA-B8-(FLRGRAYGL) (b). Colors are as in Figure 3b.
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Figure 5.
Figure 5. KK50.4 TCR-peptide interactions are dominated by the
V[  ]loops.
KK50.4 TCR contacts made by key peptide residues, the CD1
carbon of position 8 and atoms that make van der Waals contacts
with it are orange. CDR3  ,
CDR1  ,
CDR2 and
CDR3 in
'worm' format and residues in the CDR loops that make contact
with the peptide are in 'ball-and-stick' (colors are as in
Figure 3b.). Hydrogen bonds, dashed black lines; salt bridges,
gray lines; water molecules, pink spheres.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Immunol
(2006,
7,
256-264)
copyright 2006.
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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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A.R.Hofstetter,
L.C.Sullivan,
A.E.Lukacher,
and
A.G.Brooks
(2011).
Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity.
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Curr Opin Immunol,
23,
104-110.
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G.Pietra,
C.Romagnani,
C.Manzini,
L.Moretta,
and
M.C.Mingari
(2010).
The emerging role of HLA-E-restricted CD8+ T lymphocytes in the adaptive immune response to pathogens and tumors.
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J Biomed Biotechnol,
2010,
907092.
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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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R.Salerno-Goncalves,
R.Wahid,
and
M.B.Sztein
(2010).
Ex Vivo kinetics of early and long-term multifunctional human leukocyte antigen E-specific CD8+ cells in volunteers immunized with the Ty21a typhoid vaccine.
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Clin Vaccine Immunol,
17,
1305-1314.
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S.A.Joosten,
K.E.van Meijgaarden,
P.C.van Weeren,
F.Kazi,
A.Geluk,
N.D.Savage,
J.W.Drijfhout,
D.R.Flower,
W.A.Hanekom,
M.R.Klein,
and
T.H.Ottenhoff
(2010).
Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity.
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PLoS Pathog,
6,
e1000782.
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J.K.Archbold,
W.A.Macdonald,
S.Gras,
L.K.Ely,
J.J.Miles,
M.J.Bell,
R.M.Brennan,
T.Beddoe,
M.C.Wilce,
C.S.Clements,
A.W.Purcell,
J.McCluskey,
S.R.Burrows,
and
J.Rossjohn
(2009).
Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition.
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J Exp Med,
206,
209-219.
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PDB codes:
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K.W.Wucherpfennig,
M.J.Call,
L.Deng,
and
R.Mariuzza
(2009).
Structural alterations in peptide-MHC recognition by self-reactive T cell receptors.
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Curr Opin Immunol,
21,
590-595.
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B.K.Kaiser,
J.C.Pizarro,
J.Kerns,
and
R.K.Strong
(2008).
Structural basis for NKG2A/CD94 recognition of HLA-E.
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Proc Natl Acad Sci U S A,
105,
6696-6701.
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PDB code:
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D.I.Godfrey,
J.Rossjohn,
and
J.McCluskey
(2008).
The fidelity, occasional promiscuity, and versatility of T cell receptor recognition.
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Immunity,
28,
304-314.
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E.J.Collins,
and
D.S.Riddle
(2008).
TCR-MHC docking orientation: natural selection, or thymic selection?
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Immunol Res,
41,
267-294.
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E.J.Petrie,
C.S.Clements,
J.Lin,
L.C.Sullivan,
D.Johnson,
T.Huyton,
A.Heroux,
H.L.Hoare,
T.Beddoe,
H.H.Reid,
M.C.Wilce,
A.G.Brooks,
and
J.Rossjohn
(2008).
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence.
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J Exp Med,
205,
725-735.
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PDB code:
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L.C.Sullivan,
C.S.Clements,
J.Rossjohn,
and
A.G.Brooks
(2008).
The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity.
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Tissue Antigens,
72,
415-424.
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P.Marrack,
J.P.Scott-Browne,
S.Dai,
L.Gapin,
and
J.W.Kappler
(2008).
Evolutionarily conserved amino acids that control TCR-MHC interaction.
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Annu Rev Immunol,
26,
171-203.
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S.Gras,
L.Kjer-Nielsen,
S.R.Burrows,
J.McCluskey,
and
J.Rossjohn
(2008).
T-cell receptor bias and immunity.
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Curr Opin Immunol,
20,
119-125.
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A.Armirotti,
E.Millo,
and
G.Damonte
(2007).
How to discriminate between leucine and isoleucine by low energy ESI-TRAP MSn.
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J Am Soc Mass Spectrom,
18,
57-63.
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A.Goyos,
S.Guselnikov,
A.S.Chida,
L.F.Sniderhan,
S.B.Maggirwar,
H.Nedelkovska,
and
J.Robert
(2007).
Involvement of nonclassical MHC class Ib molecules in heat shock protein-mediated anti-tumor responses.
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Eur J Immunol,
37,
1494-1501.
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K.S.Park,
J.S.Park,
J.H.Nam,
D.Bang,
S.Sohn,
and
E.S.Lee
(2007).
HLA-E*0101 and HLA-G*010101 reduce the risk of Behcet's disease.
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Tissue Antigens,
69,
139-144.
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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.
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Immunity,
27,
900-911.
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PDB code:
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L.Deng,
and
R.A.Mariuzza
(2007).
Recognition of self-peptide-MHC complexes by autoimmune T-cell receptors.
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Trends Biochem Sci,
32,
500-508.
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L.Deng,
R.J.Langley,
P.H.Brown,
G.Xu,
L.Teng,
Q.Wang,
M.I.Gonzales,
G.G.Callender,
M.I.Nishimura,
S.L.Topalian,
and
R.A.Mariuzza
(2007).
Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor.
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Nat Immunol,
8,
398-408.
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PDB codes:
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M.D.Crew
(2007).
Play it in E or G: utilization of HLA-E and -G in xenotransplantation.
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Xenotransplantation,
14,
198-207.
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M.R.Goodier,
C.M.Mela,
A.Steel,
B.Gazzard,
M.Bower,
and
F.Gotch
(2007).
NKG2C+ NK cells are enriched in AIDS patients with advanced-stage Kaposi's sarcoma.
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J Virol,
81,
430-433.
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R.L.Rich,
and
D.G.Myszka
(2007).
Survey of the year 2006 commercial optical biosensor literature.
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J Mol Recognit,
20,
300-366.
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C.S.Clements,
M.A.Dunstone,
W.A.Macdonald,
J.McCluskey,
and
J.Rossjohn
(2006).
Specificity on a knife-edge: the alphabeta T cell receptor.
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Curr Opin Struct Biol,
16,
787-795.
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L.C.Sullivan,
H.L.Hoare,
J.McCluskey,
J.Rossjohn,
and
A.G.Brooks
(2006).
A structural perspective on MHC class Ib molecules in adaptive immunity.
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Trends Immunol,
27,
413-420.
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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
codes are
shown on the right.
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Links
