These results lead to two main conclusions: (i) priming with the wt virus elicits CD8+ T cells that respond relatively well to a subsequent infection with cross-reactive variant (ie 10 PR8->20 X31-NPN3A = 10 PR8-NPN3A->20 X31-NPN3A); (ii) priming with the cross-reactive variant can be detrimental as the diminished primary response may limit the full expansion of CD8+ T cells that are able to respond to the subsequent wt infection (ie 10 PR8-NPN3A->20 X31 is lower than 10 PR8->20 X31) and skew the TCR usage. Here, CD8A is linked to infection.