CLONING, CHARACTERIZATION, AND MAPPING OF HUMAN HOMOLOG OF MOUSE T-CELL DEATH-ASSOCIATED GENE

To establish immunologic autotolerance, self-reactive immature thymocy tes are eliminated by negative selection during T-cell development in the thymus, Self-reactive clones undergo apoptosis after stimulation v ia the T-cell receptor (TCR), The process of cell selection is determi ned by the dedication of the TCR for tolerogenic antigen/major histoco mpatibility complex. We have cloned a novel human gene that is highly homologous in the transmembrane and G protein-coupling domains to mous e T-cell death-associated gene 8 (TDAG8), The gene, human TDAG8 (hTDAG 8), which belongs to the G protein-couple receptor superfamily, encode s a protein of 337 amino acids. An expressed sequence tag (EST) corres ponding to hTDAG8 was identified from a human thyroid cDNA library and subsequently used to isolate a full-length genomic clone. Northern bl ot analysis revealed that the hTDAG8 gene is expressed predominantly i n lymphoid tissues, including peripheral blood leukocytes, spleen, lym ph nodes, and thymus, Stably transfected mammalian CHO cells were gene rated, and heterologous expression of hTDAG8 was confirmed by Northern blot analysis. Fluorescent in situ hybridization (FISH) revealed that hTDAG8 maps to human chromosome 14q31-32.1, a region in which abnorma lities associated with human T-cell lymphoma or leukemia are found. Ta ken together, these data implicate the hTDAG8 gene in T-cell-associate d diseases in humans, but its actual physiological and pathological ro le in the human immune system needs further investigation.