Article open access publication

Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations

PLoS ONE, Public Library of Science (PLoS), ISSN 1932-6203

Volume 12, 12, 2017

DOI:10.1371/journal.pone.0189612, Dimensions: pub.1099659697, PMC: PMC5726643, PMID: 29232408,

Affiliations

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  1. (1) University of Oxford, grid.4991.5
  2. (2) Kimberley General Hospital, Kimberley, South Africa
  3. (3) University College London, grid.83440.3b
  4. (4) Africa Health Research Institute, grid.488675.0
  5. (5) University of Copenhagen, grid.5254.6, KU
  6. (6) Royal Berkshire Hospital, grid.416094.e
  7. (7) Northampton General Hospital, grid.416531.4
  8. (8) Churchill Hospital, grid.415719.f

Description

More than 90% of children in Africa are infected with cytomegalovirus (CMV) by the age of 12 months. However, the high-frequency, immunodominant CD8+ T-cell responses that control CMV infection have not been well studied in African populations. We therefore sought to define the immunodominant CMV-specific CD8+ T-cell responses within sub-Saharan African study subjects. Among 257 subjects, we determined the CD8+ T-cell responses to overlapping peptides spanning three of the most immunogenic CMV proteins, pp65, IE-1 and IE-2, using IFN-γ ELISpot assays. A bioinformatics tool was used to predict optimal epitopes within overlapping peptides whose recognition was statistically associated with expression of particular HLA class I molecules. Using this approach, we identified 16 predicted novel CMV-specific epitopes within CMV-pp65, IE-1 and IE-2. The immunodominant pp65-specific, IE-1, IE-2 responses were all either previously well characterised or were confirmed using peptide-MHC tetramers. The novel epitopes identified included an IE-2-specific epitope restricted by HLA*B*44:03 that induced high-frequency CD8+ T-cell responses (mean 3.4% of CD8+ T-cells) in 95% of HLA-B*44:03-positive subjects tested, in one individual accounting for 18.8% of all CD8+ T-cells. These predicted novel CMV-specific CD8+ T-cell epitopes identified in an African cohort will facilitate future analyses of immune responses in African populations where CMV infection is almost universal during infancy.

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University of Copenhagen

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Times Cited: 3

Field Citation Ratio (FCR): 0.68

Relative Citation ratio (RCR): 0.36

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