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

• Published in: PloS one Vol. 12; no. 12; p. e0189612
• Main Authors: Malik, Amna, Adland, Emily, Laker, Leana, Kløverpris, Henrik, Fardoos, Rabiah, Roider, Julia, Severinsen, Mai C, Chen, Fabian, Riddell, Lynn, Edwards, Anne, Buus, Søren, Jooste, Pieter, Matthews, Philippa C, Goulder, Philip J R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.12.2017; Public Library of Science (PLoS)
• Subjects: Adult; Africa South of the Sahara; Bioinformatics; Biology and Life Sciences; CD8 antigen; CD8 lymphocytes; CD8-Positive T-Lymphocytes - immunology; Children; Cohort Studies; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus infections; Cytotoxicity; Deoxyribonucleic acid; Development and progression; DNA; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Genetic aspects; Health aspects; Health sciences; Histocompatibility antigen HLA; Hospitals; Humans; Immune response; Immunodominant Epitopes - immunology; Immunogenicity; Immunology; Infections; Interferon; Laboratories; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Male; Medical research; Medicine; Medicine and Health Sciences; People and Places; Peptides; Physiological aspects; Population studies; Populations; Pp65 protein; Proteins; Research and Analysis Methods; Studies; T cell receptors; Virology; Young Adult; γ-Interferon; South Africa; United Kingdom; Sub-Saharan Africa; Denmark
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0189612

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.