Impact of Hedgehog signalling on the T cell receptor (TCR) repertoire

We have shown that the Hedgehog signalling pathway regulates T-cell development in the thymus1,2. Sonic hedgehog (Shh) from thymic epithelial cells (TEC) signals to developing thymocytes to regulate their differentiation at key pre-T-cell receptor (pre-TCR) and TCR-dependent check-points1,2. Analysis of TCR-transgenic mice showed that Hh signalling reduced TCR signal strength during pre-TCR and TCR-induced differentiation2,3. We now plan to test the impact of these changes in TCR-signal strength induced by Hedgehog signalling on TCR repertoire selection, by next generation sequencing the TCR and TCR-chain repertoires from facs-sorted thymocyte populations at different stages of their development.