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274 a.a.
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100 a.a.
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199 a.a.
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243 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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Crystal structure of the public ra14 tcr in complex with the hcmv dominant nlv/hla-a2 epitope
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Structure:
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Hla class i histocompatibility antigen, a-2 alpha chain. Chain: h. Synonym: mhc class i antigen a 2. Engineered: yes. Mutation: yes. Hcmv pp65 fragment 495-503 (nlvpmvatv). Chain: p. Engineered: yes. Beta-2-microglobulin.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: hla, hla-a, hlaa. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Gene: b2m, beta-2 microglubulin, cdabp0092, hdcma22p. Gene: tcr.
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Resolution:
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2.80Å
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R-factor:
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0.237
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R-free:
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0.290
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Authors:
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S.Gras,X.Saulquin,J.-B.Reiser,E.Debeaupuis,K.Echasserieau, A.Kissenpfennig,F.Legoux,A.Chouquet,M.Le Gorrec,P.Machillot,B.Neveu, N.Thielens,B.Malissen,M.Bonneville,D.Housset
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Key ref:
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S.Gras
et al.
(2009).
Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.
J Immunol,
183,
430-437.
PubMed id:
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Date:
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27-Mar-09
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Release date:
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04-Aug-09
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PROCHECK
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Headers
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References
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P04439
(1A03_HUMAN) -
HLA class I histocompatibility antigen, A alpha chain from Homo sapiens
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Seq:
Struc:
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365 a.a.
274 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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J Immunol
183:430-437
(2009)
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PubMed id:
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Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.
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S.Gras,
X.Saulquin,
J.B.Reiser,
E.Debeaupuis,
K.Echasserieau,
A.Kissenpfennig,
F.Legoux,
A.Chouquet,
M.Le Gorrec,
P.Machillot,
B.Neveu,
N.Thielens,
B.Malissen,
M.Bonneville,
D.Housset.
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ABSTRACT
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Protective T cell responses elicited along chronic human CMV (HCMV) infections
are sometimes dominated by CD8 T cell clones bearing highly related or identical
public TCR in unrelated individuals. To understand the principles that guide
emergence of these public T cell responses, we have performed structural,
biophysical, and functional analyses of an immunodominant public TCR (RA14)
directed against a major HLA-A*0201-restricted HCMV Ag (pp65(495-503)) and
selected in vivo from a diverse repertoire after chronic stimulations. Unlike
the two immunodominant public TCRs crystallized so far, which focused on one
peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of
available peptide residues. The conservation of some peptide-MHC
complex-contacting amino acids by lower-affinity TCRs suggests a shared
TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of
optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal
Ag-specific response after repeated viral stimulations is based on a receptor
displaying a high structural complementarity with the entire peptide and
focusing on three peptide hotspots. This highlights key parameters underlying
the selection of a protective T cell response against HCMV infection, which
remains a major health issue in patients undergoing bone marrow transplantation.
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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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L.Kjer-Nielsen,
O.Patel,
A.J.Corbett,
J.Le Nours,
B.Meehan,
L.Liu,
M.Bhati,
Z.Chen,
L.Kostenko,
R.Reantragoon,
N.A.Williamson,
A.W.Purcell,
N.L.Dudek,
M.J.McConville,
R.A.O'Hair,
G.N.Khairallah,
D.I.Godfrey,
D.P.Fairlie,
J.Rossjohn,
and
J.McCluskey
(2012).
MR1 presents microbial vitamin B metabolites to MAIT cells.
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Nature,
491,
717-723.
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PDB code:
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J.J.Miles,
D.C.Douek,
and
D.A.Price
(2011).
Bias in the αβ T-cell repertoire: implications for disease pathogenesis and vaccination.
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Immunol Cell Biol,
89,
375-387.
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J.J.Miles,
A.M.Bulek,
D.K.Cole,
E.Gostick,
A.J.Schauenburg,
G.Dolton,
V.Venturi,
M.P.Davenport,
M.P.Tan,
S.R.Burrows,
L.Wooldridge,
D.A.Price,
P.J.Rizkallah,
and
A.K.Sewell
(2010).
Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
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PLoS Pathog,
6,
e1001198.
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PDB code:
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L.Dong,
P.Li,
T.Oenema,
C.L.McClurkan,
and
D.M.Koelle
(2010).
Public TCR use by herpes simplex virus-2-specific human CD8 CTLs.
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J Immunol,
184,
3063-3071.
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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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Links
