MODULATION OF T CELL DEVELOPMENT AND EFFECTOR FUNCTION

未成熟的双阴性胸腺细胞致力于成熟 通过重组PCRβ链基因座获得双阳性表型 诱导TCRβ蛋白表达。Pf抑制小鼠心脏功能 双阴性细胞向双阳性细胞的分化 胸腺细胞。在具体目标1中，调查员将首先确定 双阴性细胞的分期与T细胞受体的状态 PF处理细胞后的β链基因座。如果 β链基因座的重组不存在或减少， 调查人员将考虑对重组的控制和 影响TCRβ基因转录的关键事件 药物PF。如果没有β链基因的重组，或者 减少，调查员将把这一事件视为 PF的作用。然后，他将尝试识别抄本 β链基因座重组所需的因子和 其表达/活性可被PF抑制。如果TCRβ链 基因座重组不受影响，调查员将使用 适当的转基因小鼠品系，表达已安排的 β链基因在鉴定PF介导的分子中的作用 阻断双阳性胸腺细胞的发育。在第二个 特定的目标，调查人员将检查REL的表达 抗原治疗后转录因子家族成员的研究 用同源抗原和PF克隆特异性T细胞。他们将检查 这些蛋白的表达及其与DNA的结合活性 确定这些元素的表达或活性 蛋白质受到PF的影响。

Immature, double negative thymocytes commit themselves for maturation to the double positive phenotype by recombining the PCR beta chain locus and inducing the expression of TCR beta protein. PF inhibits the differentiation of double negative cells into double positive thymocytes. In specific aim 1, the investigator will first identify the stage of the double negative cells and the status of the T cell receptor beta chain locus after the treatment of the cell by PF. If the recombination of the beta chain locus is absent or reduced, the investigator will consider the control of the recombination and transcription of TCR beta locus as a critical event that is affected by the drug PF. If the recombination of the beta chain locus is absent or reduced, the investigator will consider this event as the target for the action of PF. He will then attempt to identify the transcription factors that are required for recombination of the beta chain locus and whose expression/activity is inhibited by PF. If the TCR beta chain locus recombination is unaffected, the investigator will use an appropriate transgenic mouse strain that expresses an already arranged beta chain gene in an attempt to identify the PF mediated molecular block in the development of double positive thymocytes. In the second specific aim, the investigators will examine the expression of Rel transcription factor family members after the treatment of the antigen specific T cell clone with cognate antigen and PF. They will examine the expression and the DNA binding activities of these proteins to determine whether or not the expression or the activity of these proteins is affected by PF.