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. pp. 1-10.

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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.

Item ID: 45062
Item Type: Article (Research - C1)
ISSN: 2045-2322
Additional Information:

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported license. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0

Funders: National Health and Medical Research Council (NHMRC), Queensland Cancer Fund (QCF), Australian Research Council (ARC), Monash University (MU)
Date Deposited: 10 Aug 2016 02:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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