Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the T cell repertoire

Smith, Corey, Gras, Stephanie, Brennan, Rebekah M., Bird, Nicola L., Valkenburg, Sophie A., Twist, Kelly-Anne, Burrows, Jacqueline M., Miles, John J., Chambers, Daniel, Bell, Scott, Campbell, Scott, Kedzierska, Katherine, Burrows, Scott R., Rossjohn, Jamie and Khanna, Rajiv (2014) Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the T cell repertoire. Scientific Reports, 4 3993.1-3993.10. doi:10.1038/srep03993

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Author Smith, Corey
Gras, Stephanie
Brennan, Rebekah M.
Bird, Nicola L.
Valkenburg, Sophie A.
Twist, Kelly-Anne
Burrows, Jacqueline M.
Miles, John J.
Chambers, Daniel
Bell, Scott
Campbell, Scott
Kedzierska, Katherine
Burrows, Scott R.
Rossjohn, Jamie
Khanna, Rajiv
Title Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the T cell repertoire
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2014-02
Sub-type Article (original research)
DOI 10.1038/srep03993
Open Access Status DOI
Volume 4
Start page 3993.1
End page 3993.10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2015
Language eng
Abstract 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.
Keyword Major histocompatibility complex
Organ transplant recipients
Lymphocyte clones
Hearing-loss
Infection
Immunity
Peptide
Epitope
Recognition
Responses
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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