Cloning, Characterization, and Mapping of Human Homolog of Mouse T-Cell Death-Associated Gene

摘要

To establish immunologic autotolerance, self-reactive immature thymocytes are eliminated by negative selection during T-cell development in the thymus. Self-reactive clones undergo apoptosis after stimulation via the T-cell receptor (TCR). The process of cell selection is determined by the dedication of the TCR for tolerogenic antigen/major histocompatibility complex. We have cloned a novel human gene that is highly homologous in the transmembrane and G protein-coupling domains to mouse T-cell death-associated gene 8 (TDAG8). The gene, humanTDAG8 (hTDAG8), which belongs to the G protein-couple receptor superfamily, encodes a protein of 337 amino acids. An expressed sequence tag (EST) corresponding tohTDAG8was identified from a human thyroid cDNA library and subsequently used to isolate a full-length genomic clone. Northern blot analysis revealed that thehTDAG8gene is expressed predominantly in lymphoid tissues, including peripheral blood leukocytes, spleen, lymph nodes, and thymus. Stably transfected mammalian CHO cells were generated, and heterologous expression ofhTDAG8was confirmed by Northern blot analysis. Fluorescentin situhybridization (FISH) revealed thathTDAG8maps to human chromosome 14q31-32.1, a region in which abnormalities associated with human T-cell lymphoma or leukemia are found. Taken together, these data implicate thehTDAG8gene in T-cell-associated diseases in humans, but its actual physiological and pathological role in the human immune system needs further investigation.