A NOVEL GENE-PRODUCT THAT COUPLES TCR SIGNALING TO FAS(CD95) EXPRESSION IN ACTIVATION-INDUCED CELL-DEATH

Cross-linking the TCR in T cell hybridomas induces cell apoptosis foll owing activation. This activation-induced apoptosis has been used as a model for clonal deletion of thymocytes or peripheral T cells. Anti-T CR-induced apoptosis of T cell hybridomas requires de novo macromolecu lar synthesis, including up-regulation of Fas and Fast. The Fas-FasL i nteractiom then activates the apoptosis program. To study apoptosis-sp ecific signaling processes, we generated a mutant T cell hybridoma lin e defective in induction of apoptosis, but competent to induce activat ion, upon TCR triggering. Subsequently, we cloned the gene TDAG51, whi ch restored activation-induced apoptosis when transfected into the mut ant cell line, and showed that TDAG51 expression was required for Fas expression. Thus, TDAG51 plays an essential role in induction of apopt osis by coupling TCR stimulation to Fas expression.