PLoS ONE (2017-01-01)

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

  • Amna Malik,
  • Emily Adland,
  • Leana Laker,
  • Henrik Kløverpris,
  • Rabiah Fardoos,
  • Julia Roider,
  • Mai C Severinsen,
  • Fabian Chen,
  • Lynn Riddell,
  • Anne Edwards,
  • Søren Buus,
  • Pieter Jooste,
  • Philippa C Matthews,
  • Philip J R Goulder

DOI
https://doi.org/10.1371/journal.pone.0189612
Journal volume & issue
Vol. 12, no. 12
p. e0189612

Abstract

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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.