The TCR repertoires specific for D b NP 366 and D b NPN3A appear to be quite distinct. The response overall for wt D b NP 366 + CD8 + T cells is characterised by conserved, ''public'' clonotypes that constitute the majority (83.5% in 1 0 response and 92.3% in 2 0 response) of the selected TCR repertoire [34] . These public clonotypes are not a prominent feature of the D b NPN3A + CD8 + set, being found only in 4/7 NPN3A-infected mice at very low frequency. Since we know that these TCR clonotypes are present in all B6 mice [34] , the difference presumably reflects the lower TCR avidity for D b NPN3A, as indicated by the T cell hybridoma analysis where they were shown to require 1000 times more NPN3A than NP 366 peptide for optimal stimulation. Since the public clonotypes cannot be efficiently recruited into the immune response by the mutated N3A virus, this could have created a ''hole'' in TCRs capable of recognising the mutated epitope, which subsequently can lead to a reduction in T cell immunogenicity [43] . However, though both the D b NP 366 + CD8 + and D b NPN3A + CD8 + T cell responses are characterised by quite distinct TCR repertoires, the majority are bound by both the D b NP 366 and D b NPN3A tetramers and can be detected by stimulation with either the NP 366 or the NPN3A peptides, suggesting that a clonal dissection of TCR clonotypes is needed to make a valid interpretation about the truly crossreactive CD8 + T cell responses. These findings also raise questions concerning the true correlation between pHMC-I tetramer binding in vitro and the in vivo selection of a responding TCR repertoire.