Identification of a Putative G Protein-Coupled Receptor Induced during Activation-Induced Apoptosis of T Cells

During development, self-reactive immature thymocytes are clonally deleted in the thymus, a phenomenon which establishes T cell tolerance (negative selection). It has been shown that the deletion of self-reactive 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 which genes are required during the TCR-mediated death of immature thymocytes, we sought to identify genes whose expression is increased during TCR-mediated cell death. Using the technique of differential mRNA display, we have identified a novel gene, TDAG8, which encodes a putative G protein-coupled receptor. The expression of TDAG8 is greatly induced upon activation of T cells by anti-TCR antibody or by phorbol 12-myristate 13-acetate plus ionomycin. The treatment of T cells with glucocorticoids also greatly induces the expression of TDAG8. In mice, TDAG8 is predominantly expressed in thymus and spleen. The tissue-specific expression of TDAG8 and the induction of its expression during cell death of T cells mediated by the TCR or glucocorticoids suggest that it may have a role in activation-induced cell death or differentiation of T cells.