Journal article

Molecular Imprint of Exposure to Naturally Occurring Genetic Variants of Human Cytomegalovirus on the T cell Repertoire

Corey Smith, Stephanie Gras, Rebekah M Brennan, Nicola L Bird, Sophie A Valkenburg, Kelly-Anne Twist, Jacqueline M Burrows, John J Miles, Daniel Chambers, Scott Bell, Scott Campbell, Katherine Kedzierska, Scott R Burrows, Jamie Rossjohn, Rajiv Khanna



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 rec..

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Funding Acknowledgements

We would like to thank Hanim Halim for expert technical assistance. This work was supported by the National Health and Medical Research Council (NH&MRC), Queensland Cancer Fund (QCF), and the Australian Research Council (ARC). S.G. is supported by a Monash Senior research Fellowship. R.K. and S.R.B. are supported by NH&MRC Senior Principal Research Fellowship and Senior Research Fellowship, respectively. J.R. is supported by a NH&MRC Australia Fellowship. KK and JJM are supported by a NH&MRC CDF Fellowship and SAV is an NH&MRC CJ Martin Fellow.