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Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden
The TCR repertoire of a peptide-specific HLA A11-restricted CTL
response to persistent infection with EBV was followed for a period of
57 mo. Sequencing of TCR V
and Vß chains and alanine scanning
mutagenesis analysis of 83 CTL clones isolated in five reactivation
experiments demonstrated that this repertoire is composed of at least
four distinct CTL clonotypes that are constantly reactivated from
donor’s blood and express structurally heterogeneous TCRs. Target cell
recognition and CD8 blocking experiments indicate that the four
clonotypes possess different avidity and TCR affinity for the specific
Ag. This demonstrates that at least in some individuals a heterogeneous
peptide-specific memory CTL repertoire selected by a persistent Ag can
be remarkably stable in time and accommodate a range of TCR affinities
and T cell avidities. Our results suggest that competition for the
specific Ag may be not the major force driving the maintenance of
memory CTLs and that the nature of the first antigenic challenge may
largely determine the clonal composition of memory.
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