IDENTIFICATION OF A PUTATIVE G-PROTEIN-COUPLED RECEPTOR-INDUCED DURING ACTIVATION-INDUCED APOPTOSIS OF T-CELLS

During development, self-reactive immature thymocytes are clonally del eted in the thymus, a phenomenon which establishes T cell tolerance (n egative selection). It has been shown that the deletion of self-reacti ve immature T cells in the thymus is mediated by apoptosis upon T cell receptor (TCR) engagement. Apoptosis of immature thymocytes mediated by the TCR requires the expression of a new set of genes. To define wh ich genes are required during the TCR-mediated death of immature thymo cytes, we sought to identify genes whose expression is increased durin g TCR-mediated cell death. Using the technique of differential mRNA di splay, we have identified a novel gene, TDAG8, which encodes a putativ e G protein-coupled receptor. The expression of TDAG8 is greatly induc ed upon activation of T cells by anti-TCR antibody or by phorbol 12-my ristate 13-acetate plus ionomycin. The treatment of T cells with gluco corticoids also greatly induces the expression of TDAG8. In mice, TDAG 8 is predominantly expressed in thymus and spleen. The tissue-specific expression of TDAG8 and the induction of its expression during cell d eath of T cells mediated by the TCR or glucocorticoids suggest that it may have a role in activation-induced cell death or differentiation o f T cells. (C) 1996 Academic Press, Inc.