POTENTIAL COSTIMULATORY MOLECULE

描述(改编自申请人摘要)：身份证明和 一种新的共刺激分子的特性可能在 确定导致经济衰退的机制的主要变化 与年龄相关的免疫功能丧失。肿瘤坏死的成员 因子受体(TNFR)超家族参与细胞的死亡、存活 和差异化。我们已经确定了TNFR的一名新成员 名为TR2的超级家族。TR2具有胞外富含半胱氨酸的基序 这是TNFR家族的特征，并显示出与 TNFR-II、CD40和41BB。ITS基因在淋巴样细胞中优先表达 而且是可以诱导的。阻断TR2与其配体的相互作用 抑制混合淋巴细胞反应(MLR)。我们假设TR2 与肿瘤坏死因子配体超家族的新成员相互作用并显示 共刺激功能在淋巴细胞激活中的作用。要了解其 为了验证这一假说，我们提出了三个具体目标：1 )鉴定Tr2配体并确定其分子特征 配基；2)确定TR2的生物学功能；3) 识别与细胞质尾部相关的信号分子 并对分子进行表征。我们相信我们的决心 对TR2功能的研究将加深我们对TR2功能的理解和生物学意义 肿瘤坏死因子和肿瘤坏死因子受体超家族的意义，并增强我们的能力 应用这些重要分子治疗人类自身免疫 疾病和与年龄相关的免疫功能障碍。

DESCRIPTION (adapted from applicant's abstract): Identification and characterization of a novel costimulatory molecule may be important in the determination of the primary changes in mechanisms that lead to the age-related loss of immune function. The members of the tumor necrosis factor receptor (TNFR) superfamily are involved in the cell death, survival and differentiation. We have identified a new member of the TNFR superfamily named TR2. TR2 possesses the extracellular cysteine-rich motif that is characteristic to the TNFR family, and showed similarities to TNFR-II, CD40 and 41BB. Its mRNA detected preferentially in Lymphoid cells and was inducible. Blocking the interaction between TR2 and its ligand inhibited mixed-lymphocyte-reaction (MLR). We hypothesize that TR2 interacts with a new member of TNF ligand superfamily and displays a costimulatory function in lymphocyte activation. To understand its bioactivities and to test the hypothesis, we propose three specific aims; 1 ) to identify TR2 ligand and to determine the molecular characteristics of the ligand; 2) to determine the biological functions of TR2; and 3) to identify signaling molecules associated with the cytoplasmic tail of the receptors and characterize the molecules. We believe that the determination of the function of TR2 will enhance our understanding and biological significance of TNF and TNFR superfamily, and enhance our capability to apply these important molecules for the treatment of human autoimmune diseases and age-related immune dysfunctions.