One unexpected result was that S598 exhibited both low MHC class I and low TcR avidity. Previous studies showed that this determinant exhibited low functional avidity [21] , but it was not known whether this reflected low binding to the MHC class I or to the TcR. Assuming that low affinity for MHC class I results in a low effective concentration of H-2K b /S598 complex on the cell surface, the responding T cells should be high avidity, based, primarily, on in vitro studies [37] . While the relationship between level of surface peptide and avidity of the responding T cells generated in vivo is not as clearcut [38] , there is no obvious explanation for how a peptide with low MHC class I binding also elicits a low avidity T cell response. This selection of only a subset of CD8 T cells capable of responding to S598 may partly explain why S598-primed cells do not recognize the Q600Y determinant.