 |
PDBsum entry 4hv8
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
4hv8
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Preemptive priming readily overcomes structure-Based mechanisms of virus escape.
|
|
|
Authors
|
|
S.A.Valkenburg,
S.Gras,
C.Guillonneau,
L.A.Hatton,
N.A.Bird,
K.A.Twist,
H.Halim,
D.C.Jackson,
A.W.Purcell,
S.J.Turner,
P.C.Doherty,
J.Rossjohn,
K.Kedzierska.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2013,
110,
5570-5575.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
|
|
|
|
Abstract
|
|
|
A reverse-genetics approach has been used to probe the mechanism underlying
immune escape for influenza A virus-specific CD8(+) T cells responding to the
immunodominant D(b)NP366 epitope. Engineered viruses with a substitution at a
critical residue (position 6, P6M) all evaded recognition by WT
D(b)NP366-specific CD8(+) T cells, but only the NPM6I and NPM6T mutants altered
the topography of a key residue (His155) in the MHC class I binding site.
Following infection with the engineered NPM6I and NPM6T influenza viruses, both
mutations were associated with a substantial "hole" in the naïve
T-cell receptor repertoire, characterized by very limited T-cell receptor
diversity and minimal primary responses to the NPM6I and NPM6T epitopes.
Surprisingly, following respiratory challenge with a serologically distinct
influenza virus carrying the same mutation, preemptive immunization against
these escape variants led to the generation of secondary CD8(+) T-cell responses
that were comparable in magnitude to those found for the WT NP epitope.
Consequently, it might be possible to generate broadly protective T-cell
immunity against commonly occurring virus escape mutants. If this is generally
true for RNA viruses (like HIV, hepatitis C virus, and influenza) that show high
mutation rates, priming against predicted mutants before an initial encounter
could function to prevent the emergence of escape variants in infected hosts.
That process could be a step toward preserving immune control of particularly
persistent RNA viruses and may be worth considering for future vaccine
strategies.
|
|
|
|
|
|
|
