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TCRs Differ in the Degree of Their Specificity for the Positively Selecting MHC/Peptide Ligand¹

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912 Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912

We have tested the peptide specificity of positive selection using three transgenic TCRs, originally selected on class II MHC (A^b) covalently bound with one peptide E (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.

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