In vivo overexpression of Dad1, the defender against apoptotic death-1, enhances T cell proliferation but does not protect against apoptosis

The Dad1 protein has been shown to play a role in prevention of apoptosis i n certain cell types. Dad1 is also a subunit of the oligosaccharyltransfera se enzyme complex that initiates N-linked glycosylation. It is encoded by a gene located adjacent to the TCR alpha and delta genes on mouse chromosome 14, We have investigated the role of Dad1 during T cell development and ac tivation. We observe that endogenous Dad1 levels are modulated during T cel l development to reach maximal expression In mature thymocytes. Transgenic mice that overexpress Dad1 in both the thymus and peripheral immune system have been generated. Apoptosis of thymocytes from such mice is largely unaf fected, but peripheral T cells display hyperproliferation in response to st imuli. Therefore, the linkage between the TCR and Dad1 genes may have impor tant consequences for T cell function.