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Sci Rep. 2014 Feb 10;4:3993. doi: 10.1038/srep03993.

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

Author information

1
QIMR Berghofer Medical Research Institute, Centre for Immunotherapy and Vaccine Development, Brisbane 4029 QLD Australia.
2
Department of Biochemistry & Molecular Biology, School of Biomedical Sciences, Monash University, Clayton 3800 VIC Australia.
3
Department of Microbiology and Immunology, The University of Melbourne, Parkville 3010 VIC Australia.
4
1] QIMR Berghofer Medical Research Institute, Centre for Immunotherapy and Vaccine Development, Brisbane 4029 QLD Australia [2] Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
5
1] Queensland Lung Transplant Service The Prince Charles Hospital, Brisbane 4032 QLD Australia [2] School of Medicine, The University of Queensland Herston 4006 QLD Australia.
6
Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane 4032 QLD Australia.
7
Renal Transplant Unit, Princess Alexandra Hospital, Brisbane 4102 QLD Australia.
8
1] Department of Biochemistry & Molecular Biology, School of Biomedical Sciences, Monash University, Clayton 3800 VIC Australia [2] Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

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.

PMID:
24509977
PMCID:
PMC3918921
DOI:
10.1038/srep03993
[Indexed for MEDLINE]
Free PMC Article

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