Modulating the immunogenicity of subdominant CTL determinants could potentially lead to the development of more efficacious vaccines that are more broadly protective and prevent or minimize the appearance of variant viruses that have mutated in dominant epitopes targeted by high-avidity CTL responses. Enhancement strategies, which result in augmented responses to the native, subdominant epitope, have been described for both MHC class I and class II-restricted determinants, whereby the most common approaches involve generating a series of conserved and non-conserved mutations at MHC anchor residues, followed by an empiric determination of whether each individual substitution augments T cell effector function [12] . Furthermore, evaluating the effect of epitope enhancement in vivo has generally been achieved via heterologous infection systems [13] [14] [15] . Thus, while these results demonstrate proof of principle, direct evidence for enhanced protection against autologous microbial infection in vivo is lacking. The design of heteroclitic determinants in which non-MHC anchor residues are targeted for substitution are also usually determined empirically. Studies of heteroclitic tumor epitopes have demonstrated the clinical utility of such determinants [16, 17] . Notably, however, there are no well defined examples of viral epitopes which demonstrate enhanced immunity and the molecular basis for the enhanced immunogenicity is not well understood.