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PDBsum entry 4l8c
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Immune system
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PDB id
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4l8c
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References listed in PDB file
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Key reference
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Title
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Acute emergence and reversion of influenza a virus quasispecies within cd8+ t cell antigenic peptides.
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Authors
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S.A.Valkenburg,
S.Quiñones-Parra,
S.Gras,
N.Komadina,
J.Mcvernon,
Z.Wang,
H.Halim,
P.Iannello,
C.Cole,
K.Laurie,
A.Kelso,
J.Rossjohn,
P.C.Doherty,
S.J.Turner,
K.Kedzierska.
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Ref.
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Nat Commun, 2013,
4,
2663.
[DOI no: ]
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PubMed id
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Abstract
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Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a
degree of cross-strain protection that is potentially subverted by mutation.
Here we describe the sequential emergence of such variants within CTL epitopes
for a persistently infected, immunocompromised infant. Further analysis in
immunodeficient and wild-type mice supports the view that CTL escape variants
arise frequently in influenza, accumulate with time and revert in the absence of
immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance
of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity
influence the nature of these de novo mutants. Structural characterization of
dominant escape variants shows how the peptide-MHCI interaction is modified to
affect variant-MHCI stability. The mechanism of influenza virus escape thus
looks comparable to that recognized for chronic RNA viruses like HIV and HCV,
suggesting that immunocompromised patients with prolonged viral infection could
have an important part in the emergence of influenza quasispecies.
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