Discovery of a monoclonal, high-affinity CD8+ T cell clone following
natural hepatitis C virus infection
Abstract
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.