Using influenza A virus infection of B6 mice [20] , we showed previously that virus variants with mutations at critical solventexposed residues that are important for TCR binding can generate effective but non-cross-reactive CD8 + CTL responses to what are essentially new epitopes [21, 22] . This raises the possibility that it might be worthwhile to think in terms of vaccinating against likely virus escape mutants. The present analysis focuses on the crossreactive (to wt D b NP 366 ) CD8 + T cell response to the mutant D b NPN3A epitope [22] formed by substitution of the partially solvent exposed, and non-prominent for TCR binding, residue at position (P) 3 of the influenza NP 366-374 peptide [21, 23] . The findings have implications for vaccines to combat virus mutants and tumour escape variants, and suggest that immunisation against likely cross-reactive variants would have to be carefully evaluated to see if the strategy is worthwhile.