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PDBsum entry 4qrs
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Immune system
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PDB id
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4qrs
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References listed in PDB file
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Key reference
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Title
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Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the t cell repertoire.
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Authors
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C.Smith,
S.Gras,
R.M.Brennan,
N.L.Bird,
S.A.Valkenburg,
K.A.Twist,
J.M.Burrows,
J.J.Miles,
D.Chambers,
S.Bell,
S.Campbell,
K.Kedzierska,
S.R.Burrows,
J.Rossjohn,
R.Khanna.
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Ref.
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Sci Rep, 2014,
4,
3993.
[DOI no: ]
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PubMed id
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Abstract
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Exposure to naturally occurring variants of herpesviruses in clinical settings
can have a dramatic impact on anti-viral immunity. Here we have evaluated the
molecular imprint of variant peptide-MHC complexes on the T-cell repertoire
during human cytomegalovirus (CMV) infection and demonstrate that primary
co-infection with genetic variants of CMV was coincident with development of
strain-specific T-cell immunity followed by emergence of cross-reactive
virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly
conserved public T cell repertoire, while T cells directed towards specific
genetic variants displayed oligoclonal repertoires, unique to each individual. T
cell recognition foot-print and pMHC-I structural analyses revealed that the
cross-reactive T cells accommodate alterations in the pMHC complex with a
broader foot-print focussing on the core of the peptide epitope. These findings
provide novel molecular insight into how infection with naturally occurring
genetic variants of persistent human herpesviruses imprints on the evolution of
the anti-viral T-cell repertoire.
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