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PDBsum entry 2zol
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Immune system
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PDB id
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2zol
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Contents |
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* Residue conservation analysis
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J Immunol
180:3926-3937
(2008)
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PubMed id:
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Structural and biological basis of CTL escape in coronavirus-infected mice.
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N.S.Butler,
A.Theodossis,
A.I.Webb,
M.A.Dunstone,
R.Nastovska,
S.H.Ramarathinam,
J.Rossjohn,
A.W.Purcell,
S.Perlman.
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ABSTRACT
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Cytotoxic T lymphocyte escape occurs in many human infections, as well as mice
infected with the JHM strain of mouse hepatitis virus, which exhibit CTL escape
variants with mutations in a single epitope from the spike glycoprotein (S510).
In all CTL epitopes prone to escape, only a subset of all potential variants is
generally detected, even though many of the changes that are not selected would
result in evasion of the T cell response. It is postulated that these unselected
mutations significantly impair virus fitness. To define more precisely the basis
for this preferential selection, we combine x-ray crystallographic studies of
the MHC class I (D(b))/S510 complexes with viral reverse genetics to identify a
prominent TCR contact residue (tryptophan at position 4) prone to escape
mutations. The data show that a mutation that is commonly detected in
chronically infected mice (tryptophan to arginine) potently disrupts the
topology of the complex, explaining its selection. However, other mutations at
this residue, which also abrogate the CTL response, are never selected in vivo
even though they do not compromise virus fitness in acutely infected animals or
induce a significant de novo CTL response. Thus, while structural analyses of
the S510/D(b) complex provide a strong basis for why some CTL escape variants
are selected, our results also show that factors other than effects on virus
fitness limit the diversification of CD8 T cell epitopes.
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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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H.Kashiwazaki,
R.Nomura,
S.Matsuyama,
F.Taguchi,
and
R.Watanabe
(2011).
Spongiform degeneration induced by neuropathogenic murine coronavirus infection.
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Pathol Int,
61,
184-191.
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A.Theodossis,
C.Guillonneau,
A.Welland,
L.K.Ely,
C.S.Clements,
N.A.Williamson,
A.I.Webb,
J.A.Wilce,
R.J.Mulder,
M.A.Dunstone,
P.C.Doherty,
J.McCluskey,
A.W.Purcell,
S.J.Turner,
and
J.Rossjohn
(2010).
Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition.
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Proc Natl Acad Sci U S A,
107,
5534-5539.
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S.A.Valkenburg,
S.Gras,
C.Guillonneau,
N.L.La Gruta,
P.G.Thomas,
A.W.Purcell,
J.Rossjohn,
P.C.Doherty,
S.J.Turner,
and
K.Kedzierska
(2010).
Protective efficacy of cross-reactive CD8+ T cells recognising mutant viral epitopes depends on peptide-MHC-I structural interactions and T cell activation threshold.
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PLoS Pathog,
6,
0.
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PDB code:
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N.S.Butler,
A.Theodossis,
A.I.Webb,
R.Nastovska,
S.H.Ramarathinam,
M.A.Dunstone,
J.Rossjohn,
A.W.Purcell,
and
S.Perlman
(2008).
Prevention of cytotoxic T cell escape using a heteroclitic subdominant viral T cell determinant.
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PLoS Pathog,
4,
e1000186.
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PDB codes:
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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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}
}
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