Malik, A;
Adland, E;
Laker, L;
Klenferpris, H;
Fardoos, R;
Roider, J;
Severinsen, MC;
... Goulder, PJR; + view all
(2017)
Immunodominant cytomegalovirus-specific CD8+T-cell responses in sub-Saharan African populations.
PLoS ONE
, 12
(12)
, Article e0189612. 10.1371/journal.pone.0189612.
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Abstract
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 subSaharan 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.
| Type: | Article |
|---|---|
| Title: | Immunodominant cytomegalovirus-specific CD8+T-cell responses in sub-Saharan African populations |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0189612 |
| Publisher version: | https:// doi.org/10.1371/journal.pone.0189612 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, CD8(+) T-CELLS, HLA ALLELES, DISEASE PROGRESSION, CTL EPITOPES, INFECTION, IDENTIFICATION, HIV, SEROPREVALENCE, RECOGNITION, INFLATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10064138 |
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