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

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Version 2 2023-06-12, 06:37
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journal contribution
posted on 2023-06-12, 06:37 authored by Andrew Sylwester, Kate Z Nambiar, Stefano Caserta, Paul Klenerman, Louis J Picker, Florian KernFlorian Kern
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 responders 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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Mechanisms of Ageing and Development

ISSN

0047-6374

Publisher

Elsevier

Volume

158

Page range

14-22

Department affiliated with

  • BSMS Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-03-11

First Open Access (FOA) Date

2017-03-01

First Compliant Deposit (FCD) Date

2016-11-10

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