Thinking about this in terms of possible vaccination strategies for use against rapidly changing viruses or tumor epitopes, it appears that priming with cross-reactive mutants that have characteristics comparable to NPN3A would be of no benefit (or even could be detrimental as evidenced by delayed viral clearance) as the same level of T cell immunity against such mutants can be elicited by exposure to the wt epitope. On the other hand, changes like the non-cross-reactive NP-M6A mutation [22] that induce a completely novel, high quality response might merit incorporation in an experimental vaccine or immunotherapy strategy. Overall, working out the topographical constraints that determine these differential response profiles would seem eminently worthwhile.