alpha beta TCRs differ in the degree of their specificity for the positively selecting MHC/peptide ligand

We have tested the peptide specificity of positive selection using three tr ansgenic alpha beta TCRs originally selected on class II MHC (A(b)) covalen tly bound with one peptide E alpha (52-68) (Ep). The transgenic TCR specifi c for the cytochrome c-derived (43-58) peptide was selected on Ab bound wit h different arrays of endogenous peptides or the analogue of Ep covalently bound to A(b), hut not on the original A(b)Ep complex. In contrast, transge nic TCRs specific for two different analogues of the Ep peptide and Ab did not mature as CD4+ T cells in various thymic environments, including the A( b)EpIi(-) mice, These results show that TCRs can be promiscuous or specific for the selecting MHC/peptide complex, and suggest that in mice described in this study transgenic expression of the TCR changes the original require ments for the positively selecting MHC/peptide complex. Future studies will . determine whether the latter phenomenon is general or specific for this s ystem.