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PCR β链基因座， 诱导TCR β蛋白表达。 PF抑制了 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，研究人员将首先确定 双阴性细胞的阶段和T细胞受体的状态 在用PF处理细胞后， 当β链基因座的重组不存在或减少时， 研究者将考虑控制重组， TCR β基因座的转录是受以下因素影响的关键事件： 如果β链基因座的重组不存在或 降低，则研究者将此事件视为 然后，他将尝试识别转录 β链基因座重组所需的因子， 其表达/活性被PF抑制。如果TCR β链 基因座重组不受影响，研究者将使用 合适的转基因小鼠品系，其表达已经排列的 β链基因，试图确定PF介导的分子 阻断双阳性胸腺细胞的发育。 在第二 具体的目的，研究人员将检查Rel的表达 抗原处理后转录因子家族成员 具有同源抗原和PF特异性T细胞克隆。他们将检查 这些蛋白质的表达和DNA结合活性， 确定这些基因的表达或活性是否 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.