HCV-specific CD8+ T cells are abundant in HCV-seronegatives but show private TCR repertoires
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1
Hannover Medical School, Department of Gastroenterology, Hepatology, Endocrinology, Germany
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2
Hannover Biomedical Research School (HBRS), Germany
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3
Hannover Medical School, Department of Clinical Immunology and Rheumatology, Germany
Introduction: Presence of virus-specific CD8+ T cells has been frequently detected in uninfected individuals, but detailed characteristics have so far been poorly defined. This study aimed to detect, phenotype, analyze the T cell receptor (TCR) repertoire and functionally characterize T cells specific for the immunodominant HCV NS3-1073 epitope in HCV seronegative individuals (HCV-SNs) with different risk factors of HCV exposure.
Results: HCV NS3-1073-specific CD8+ T cells were frequently detected in HCV-SNs by ex vivo tetramer enrichment. These cells show a highly variable memory phenotype (CD45RA- 5-42%). After in vitro expansion, significant HCV NS3-1073 specific T cells were detected in 31.8% (21/66) of HCV-SNs. Unexpectedly, here we observed no differences between the different risk groups. The TCR α and β repertoire of sorted NS3-1073 specific CD8+T cells demonstrated a high variability between individuals. Some HCV-SNs showed highly oligoclonal TCRs while others were rather diverse. Of note, some TCR β repertoires included CDR3 motifs that could also be found in patients with acute HCV infection.
Conclusion: Our data show that in HCV uninfected individuals memory T cells specific for HCV NS3-1073 are abundant and display private TCR specificities. One mechanism for this phenomenon can be TCR cross-reactivity as previously shown for this epitope. The oligoclonal TCRs and the similarity of CDR3 motifs between HCV-SNs and acute HCV patients supports this hypothesis. Thus, the presence and variability of pre-existing cross-reactive memory T cells may help to explain the varying natural outcomes of HCV infection.
Keywords:
HCV seronegative,
CD8+ T cells,
memory T cells,
T cell receptor repertoire,
heterologous immunity
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Zhang
S,
Bakshi
R,
Fytili
P,
Jacobs
R,
Manns
MP,
Wedemeyer
H,
Kraft
A,
Cornberg
M and
Schlaphoff
V
(2013). HCV-specific CD8+ T cells are abundant in HCV-seronegatives but show private TCR repertoires.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01000
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Received:
28 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Markus Cornberg, Hannover Medical School, Department of Gastroenterology, Hepatology, Endocrinology, Hannover, Germany, Cornberg.Markus@mh-hannover.de
Dr. Verena Schlaphoff, Hannover Medical School, Department of Gastroenterology, Hepatology, Endocrinology, Hannover, Germany, Schlaphoff.Verena@mh-hannover.de