title: A new perspective of the structural complexity of HCMV-specific T-cell responses.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Vaccine & Gene Therapy Institute, Oregon Health & Science University West Campus, Beaverton, OR 97006, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sylwester
authors.affiliation: Division of Medicine, Brighton and Sussex Medical School, Brighton BN1 9PX, United Kingdom.
authors.forename: Kate Z
authors.initials: KZ
authors.lastname: Nambiar
authors.affiliation: Division of Medicine, Brighton and Sussex Medical School, Brighton BN1 9PX, United Kingdom.
authors.forename: Stefano
authors.initials: S
authors.lastname: Caserta
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: Vaccine & Gene Therapy Institute, Oregon Health & Science University West Campus, Beaverton, OR 97006, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.affiliation: Division of Medicine, Brighton and Sussex Medical School, Brighton BN1 9PX, United Kingdom. Electronic address: f.kern@bsms.ac.uk.
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
keywords: Cytomegalovirus; Host response; T-cell memory-inflation; T-cells