Tetramer enrichment reveals the presence of phenotypically diverse hepatitis C virus-specific CD8+T cells in chronic infection
Abstract: Virus-specific CD8+ T cells are rarely detectable ex vivo by conventional methods during chronic hepatitis C virus (HCV) infection. In this study, however, we were able to detect and characterize HCV-specific CD8+ T cells in all chronically HCV genotype 1a-infected, HLA-A*02:01-positive patients analyzed by performing major histocompatibility complex (MHC) class I tetramer enrichment. Two-thirds of these enriched HCV-specific CD8+ T-cell populations displayed an effector memory phenotype, whereas, surprisingly, one-third displayed a naive-like phenotype despite ongoing viral replication. CD8+ T cells with an effector memory phenotype could not expand in vitro, suggesting exhaustion of these cells. Interestingly, some of the naive-like CD8+ T cells proliferated vigorously upon in vitro priming, whereas others did not. These differences were linked to the corresponding viral sequences in the respective patients. Indeed, naive-like CD8+ T cells from patients with the consensus sequence in the corresponding T-cell epitope did not expand in vitro. In contrast, in patients displaying sequence variations, we were able to induce HCV-specific CD8+ T-cell proliferation, which may indicate infection with a variant virus. Collectively, these data reveal the presence of phenotypically and functionally diverse HCV-specific CD8+ T cells at very low frequencies that are detectable in all chronically infected patients despite viral persistence
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Journal of virology. - 89 (2015) , 25-34, ISSN: 0022-538X
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2019
- Urheber
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Nitschke, Katja
Flecken, Tobias
Schmidt, Julia
Gostick, Emma
Marget, Matthias
Neumann-Haefelin, Christoph
Blum, Hubert E.
Price, David A.
Thimme, Robert
- Beteiligte Personen und Organisationen
- DOI
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10.1128/jvi.02242-14
- URN
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urn:nbn:de:bsz:25-freidok-1202672
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:59 MESZ
Datenpartner
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Beteiligte
- Nitschke, Katja
- Flecken, Tobias
- Schmidt, Julia
- Gostick, Emma
- Marget, Matthias
- Neumann-Haefelin, Christoph
- Blum, Hubert E.
- Price, David A.
- Thimme, Robert
- Universitätsklinikum Freiburg. Klinik für Innere Medizin II
- Universität
Entstanden
- 2019