Transgenic expression of Ly-49A in thymocytes alters repertoire selection

A T cell-specific Ly-49A transgene inhibits TCR-mediated activation in the presence of H-2D(d). Expression of this transgene by developing thymocytes impairs negative selection evidenced by a failure to delete potentially aut oreactive T cells and development of a graft-vs-host-disease-like syndrome. In mice carrying both the Ly-49A and a class II-restricted TCR transgene, positive selection was lost, but only when H-2D(d) was present on thymic ep ithelium, These results are consistent with models suggesting that thymic s election is dependent on the perceived intensity of TCR signaling. More int erestingly, these results show that Ly-49A does not simply provide a strict on/off switch for T cell responses. Since Ly-49A may shift the signaling t hreshold of TCR-induced triggering, inducible expression of Ly-49A may regu late peripheral memory/activated T cells by raising the threshold for T cel l reactivation.