Cargando…

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

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-sp...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726643/
https://www.ncbi.nlm.nih.gov/pubmed/29232408
http://dx.doi.org/10.1371/journal.pone.0189612
_version_ 1783285732219027456
author 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.
author_facet 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.
author_sort Malik, Amna
collection PubMed
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.
format Online
Article
Text
id pubmed-5726643
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-57266432017-12-22 Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations 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. PLoS One Research Article 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. Public Library of Science 2017-12-12 /pmc/articles/PMC5726643/ /pubmed/29232408 http://dx.doi.org/10.1371/journal.pone.0189612 Text en © 2017 Malik et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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.
Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations
title Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations
title_full Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations
title_fullStr Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations
title_full_unstemmed Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations
title_short Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations
title_sort immunodominant cytomegalovirus-specific cd8+ t-cell responses in sub-saharan african populations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726643/
https://www.ncbi.nlm.nih.gov/pubmed/29232408
http://dx.doi.org/10.1371/journal.pone.0189612
work_keys_str_mv AT malikamna immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT adlandemily immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT lakerleana immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT kløverprishenrik immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT fardoosrabiah immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT roiderjulia immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT severinsenmaic immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT chenfabian immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT riddelllynn immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT edwardsanne immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT buussøren immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT joostepieter immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT matthewsphilippac immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations
AT goulderphilipjr immunodominantcytomegalovirusspecificcd8tcellresponsesinsubsaharanafricanpopulations