αβTCRs Differ in the Degree of Their Specificity for the Positively Selecting MHC/Peptide Ligand

Abstract

We have tested the peptide specificity of positive selection using three transgenic αβTCRs, originally selected on class II MHC (Ab) covalently bound with one peptide Eα (52–68) (Ep). The transgenic TCR specific for the cytochrome c-derived (43–58) peptide was selected on Ab bound with different arrays of endogenous peptides or the analogue of Ep covalently bound to Ab, but not on the original AbEp complex. In contrast, transgenic 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 AbEpIi− 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.