Modulation of TCRβ surface expression during TCR revision

► Through TCR revision, autoreactive TCRs are replaced by those generated through post-thymic DNA rearrangement. ► Downmodulation of surface TCR expression initiates RAG re-expression and TCR revision. ► In Vβ5 transgenic mice, loss of surface TCR is not mediated by transgene loss or diminished expression. ► Downregulation of surface TCR expression occurs in two stages, only one of which requires tolerogen expression. TCR revision is a tolerance mechanism by which self-reactive TCRs expressed by mature CD4 + peripheral T cells are replaced by receptors encoded by genes generated by post-thymic DNA rearrangement. The downmodulation of surface TCR expression initiates TCR revision, and serves as a likely trigger for the induction of the recombinase machinery. We show here in a Vβ5 transgenic mouse model system that downregulation of the self-reactive transgene-encoded TCR is not maintained by transgene loss or diminished transcription or translation. The downregulation of surface TCR expression likely occurs in two stages, only one of which requires tolerogen expression.