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Discovery of a monoclonal, high-affinity CD8+ T cell clone following natural hepatitis C virus infection
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  • Curtis Cai,
  • Elizabeth Keoshkerian,
  • Kristof Wing,
  • Jerome Samir,
  • Manuel Effenberger,
  • Kilian Schober,
  • Rowena Bull,
  • Andrew Lloyd,
  • Dirk Busch,
  • Fabio Luciani
Curtis Cai
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Elizabeth Keoshkerian
The Kirby Institute
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Kristof Wing
Technical University of Munich
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Jerome Samir
UNSW Sydney
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Manuel Effenberger
Technical University of Munich
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Kilian Schober
Friedrich-Alexander-Universität Erlangen-Nürnberg
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Rowena Bull
University of New South Wales School of Medical Sciences
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Andrew Lloyd
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Dirk Busch
Technische Universität München
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Fabio Luciani

Corresponding Author:[email protected]

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CD8+ T cells recognising their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide-MHC (pMHC) complex. Advances in single-cell sequencing have increased accessibility towards identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T cell population with specificity for a hepatitis C virus (HCV)-derived HLA class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent prior to infection and underwent expansion and stable maintenance for at least two years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterised by an unusually long dissociation time (half-life = 794 seconds and koff = 5.73×10-4) for its target antigen when compared to previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggest that high-affinity TCR-pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalised immunotherapies.
26 Feb 2024Submitted to Immunology & Cell Biology
27 Feb 2024Assigned to Editor
27 Feb 2024Submission Checks Completed
27 Feb 2024Reviewer(s) Assigned