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A new perspective of the structural complexity of HCMV-specific T-cell responses

Sylwester, Andrew; Nambiar, Kate Z.; Caserta, Stefano; Klenerman, Paul; Picker, Louis J.; Kern, Florian


Andrew Sylwester

Kate Z. Nambiar

Paul Klenerman

Louis J. Picker

Florian Kern


© 2016 The Authors Background In studies exploring the effects of HCMV infection on immune system aging (‘immunosenescence’), after organ transplantation or in other settings, HCMV-specific T-cell responses are often assessed with respect to purportedly ‘immunodominant’ protein subunits. However, the response structure in terms of recognized antigens and response hierarchies (architecture) is not well understood and actual correlates of immune protection are not known. Methods We explored the distribution of T-cell response sizes and dominance hierarchies as well as response breadth in 33 HCMV respon ders with respect to  > 200 HCMV proteins. Results At the individual responder level HCMV-specific T-cell responses were generally arranged in clear dominance hierarchies; interestingly, the number of proteins recognized by an individual correlated closely with the size of their biggest response. Target-specificity varied considerably between donors and across hierarchy levels with the presence, size, and hierarchy position of responses to purportedly ‘immunodominant’ targets being unpredictable. Conclusions Predicting protective immunity based on isolated HCMV subunit-specific T-cell responses is questionable in light of the complex architecture of the overall response. Our findings have important implications for T-cell monitoring, intervention strategies, as well as the application of animal models to the understanding of human infection.


Sylwester, A., Nambiar, K. Z., Caserta, S., Klenerman, P., Picker, L. J., & Kern, F. (2016). A new perspective of the structural complexity of HCMV-specific T-cell responses. Mechanisms of ageing and development, 158, 14-22.

Journal Article Type Article
Acceptance Date Mar 3, 2016
Publication Date 2016-09
Deposit Date Feb 22, 2018
Publicly Available Date Mar 20, 2018
Journal Mechanisms of Ageing and Development
Print ISSN 0047-6374
Electronic ISSN 1872-6216
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 158
Pages 14-22
Keywords Developmental Biology; Ageing
Public URL
Publisher URL
Additional Information This article is maintained by: Elsevier; Article Title: A new perspective of the structural complexity of HCMV-specific T-cell responses; Journal Title: Mechanisms of Ageing and Development; CrossRef DOI link to publisher maintained version:; Content Type: article; Copyright: © 2016 The Authors. Published by Elsevier Ireland Ltd.


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