Generation of CD8(+) T cell memory in response to low, high, and excessive levels of epitope.

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-gamma 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-gamma-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.