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

Abstract

© 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.

Citation

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. https://doi.org/10.1016/j.mad.2016.03.002

• 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
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 158
• Pages: 14-22
• DOI: https://doi.org/10.1016/j.mad.2016.03.002
• Keywords: Developmental Biology; Ageing
• Public URL: https://hull-repository.worktribe.com/output/620528
• Publisher URL: http://sro.sussex.ac.uk/60019/
• 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: http://dx.doi.org/10.1016/j.mad.2016.03.002; Content Type: article; Copyright: © 2016 The Authors. Published by Elsevier Ireland Ltd.
• Contract Date: Feb 22, 2018