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Immunodominance of HLA-A2-restricted Hepatitis C virus-specific CD8+ T cell responses is linked to naïve-precursor frequency

The impact of naïve-precursor frequency on human virus-specific CD8+ T cell immunodominance is not well understood. Using a recently developed major histocompatibility complex (MHC) class I tetramer enrichment protocol, we found a conserved hierarchy and a >10-fold difference in naïve-precursor...

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Main Authors: Schmidt, Julia (Author) , Neumann-Haefelin, Christoph (Author) , Altay, Tayibe (Author) , Gostick, Emma (Author) , Price, David A. (Author) , Lohmann, Volker (Author) , Blum, Hubert E. (Author) , Thimme, Robert (Author)
Format: Article (Journal)
Language:English
Published: 21 April 2011
In: Journal of virology
Year: 2011, Volume: 85, Issue: 10, Pages: 5232-5236
ISSN:1098-5514
DOI:10.1128/JVI.00093-11
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1128/JVI.00093-11
Verlag, lizenzpflichtig, Volltext: https://journals.asm.org/doi/10.1128/JVI.00093-11
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Author Notes:Julia Schmidt, Christoph Neumann-Haefelin, Tayibe Altay, Emma Gostick, David A. Price, Volker Lohmann, Hubert E. Blum, and Robert Thimme

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520 |a The impact of naïve-precursor frequency on human virus-specific CD8+ T cell immunodominance is not well understood. Using a recently developed major histocompatibility complex (MHC) class I tetramer enrichment protocol, we found a conserved hierarchy and a >10-fold difference in naïve-precursor frequencies across three HLA-A2-restricted hepatitis C virus (HCV)-specific epitopes. Importantly, the NS31406 epitope with the highest naïve-precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both ex vivo and after in vitro stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve-precursor frequency. 
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