The biological significance of the heteroclitic Q600Y determinant was shown by its ability to protect JHMV-infected mice from CTL escape at S510 and to diminish clinical disease. This was important to demonstrate because other studies, using tumor models, have shown that immunogenicity and tumor recognition are not necessarily concordant [39] . Mutations resulting in CTL escape occur most commonly in determinants that are exposed to high selective pressure [40] [41] [42] and outgrowth of CTL escape variants is efficiently suppressed by effective and rapid virus clearance [43] [44] [45] [46] , as occurs in mice infected with rJ.S Q600Y . Thus, even though CTL escape is not detected in normal mice infected with LCMV or influenza, escape does occur when mice transgenic for a single LCMV-specific TcR are infected with high amounts of virus [44, 47] . Under these conditions, the immune response is highly focused on a single CD8 T cell determinant and virus replication continues for extended periods of time, facilitating mutation at the targeted determinant.