Virus escape mutants are well documented for persistent infections and constitute a major problem for CD8 + T cellmediated control and vaccine design [3, 4, 5, 6, 7, 8, 9] . With regard to the influenza A viruses, mutational changes driven by CD8 + cytotoxic T lymphocytes (CTLs) are unlikely to result in long-term persistence within the individual, as other mechanisms (particularly antibody) can ultimately mediate virus clearance [10] . Even so, the fact that such mutants can be found in nature suggests that influenza virus-specific CTLs are of protective value. Perhaps this reflects that the infection of new subjects favours the selection of mutant viruses that are more slowly controlled (and thus shed for longer), particularly in the face of a seasonal ''bottleneck'' where much of the population is already immune [11] . In humans, influenza escape variants have been observed for CD8 + T cell epitopes presented in context of several HLAs, including HLA-B8, HLA-B27 and HLA-B35 [12, 13, 14, 15, 16, 17, 18, 19] . The immunogenic peptides can be modified at an MHC anchor residue, resulting in defective binding to the MHC-I glycoprotein, or at a TCR contact site. Mutations at TCR contact residues lead to partial (cross-reactive) or total (non-cross-reactive) loss of recognition by wt CD8 + T cells [13] , with some variants eliciting epitopespecific CD8 + T cell responses that are both novel and of substantial magnitude [12] .