Potential interventions to directly manipulate host-pathogen interactions and thereby diminish CTL escape variant selection are often difficult to evaluate since most examples of CTL escape occur in infected humans or non-human primates. By contrast, mice persistently infected with mouse hepatitis virus (MHV) strain JHM (JHMV) serve as a useful system for investigating anti-viral CTL responses and CTL escape [18] [19] [20] . Two JHMV-derived CTL epitopes are recognized in C57BL/6 (B6) mice. The immunodominant H-2D b -restricted CTL epitope (S510, CSLWNGPHL, spanning residues 510-518 of the Spike (S) glycoprotein) elicits a highmagnitude, high-avidity CTL response that drives virus diversification during persistent infection [18] [19] [20] [21] [22] . A second subdominant CTL epitope, S598 (H-2K b -restricted, RCQIFANI, spanning residues 598-605 of the S glycoprotein) also elicits an appreciable CTL response [21] ; however, S598-specific CTL exhibit ,100-fold lower functional avidity and do not protect from CTL escape in S510. The presence of a readily mutable dominant and a subdominant epitope with high and low functional avidity, respectively, in JHMV-infected mice is useful for investigating both epitope enhancement and approaches to diminishing CTL escape. Consistent with this notion, we have previously shown that the introduction of a second dominant CD8 T cell epitope into the JHMV genome (GP33 from lymphocytic choriomeningitis virus (LCMV)) protected mice from the development of CTL escape in S510 and enhanced virus clearance [22] .