Negative selection of thymocytes expressing the D10 TCR.

We have analyzed the patterns of positive and negative selection of thymocytes expressing the T cell antigen receptor (TCR) from the D10.G4.1 T cell clone. This TCR confers reactivity to several non-self MHC class II alleles with a remarkably broad range of avidities. Therefore, negative selection can be studied when induced by high-, intermediate-, or low-avidity interactions with endogenous peptide-MHC complexes, all within the same TCR transgenic system. These data directly demonstrate that MHC class II-peptide ligands that fail to activate mature T cells can promote negative selection of immature thymocytes. Additionally, we show that negative selection of thymocytes can occur at two distinct "time points" during development depending on the avidity of the TCR for the MHC-peptide complex. Finally, we show that the self-peptide repertoire plays a significant role in selection because alteration of the self-peptide repertoire by disruption of the H2-Ma gene drastically alters selection of D10 TCR-expressing thymocytes.