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Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107
The magnitude of a virus-specific memory CTL population can
dramatically influence the outcome of secondary infections, yet little
is known about the determinants of memory size. We investigated the
impact of epitope levels on CTL memory generation by using a
recombinant vaccinia virus system that allows for a broad range of
epitope expression with the same infectious dose of virus. The size of
the memory pool was examined using MHC class I/peptide tetramer
staining and IFN-
ELISPOT analysis following priming with viruses
expressing low, high, or excessive epitope levels. The size of the
epitope-specific CD8+ T cell memory population correlates
with Ag dose at the low and high levels of epitope expression. However,
at excessive epitope levels, the number of functional,
IFN--producing, epitope-specific memory cells is significantly
reduced compared with the number of tetramer+ cells. These
results demonstrate that the level of epitope expressed during an acute
viral infection in vivo can dramatically influence CTL memory size.
Furthermore, when epitope is overexpressed, the quality of the response
can be adversely affected. Therefore, epitope expression level is an
important consideration when developing approaches to optimize CTL
memory induction.
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