α/βTCRs 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 transgenic αβTCRs, originally selected on class II MHC (A^b) covalently bound with one peptide Eα (52-68) (Ep). The transgenic TCR specific for the cytochrome c-derived (43-58) peptide was selected on A^b bound with different arrays of endogenous peptides or the analogue of Ep covalently bound to A^b, but not on the original A^bEp complex. In contrast, transgenic TCRs specific for two different analogues of the Ep peptide and A^b did not mature as CD4⁺ T cells in various thymic environments, including the A^bEpIi^- 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 requirements for the positively selecting MHC/peptide complex. Future studies will determine whether the latter phenomenon is general or specific for this system.