PLATELET AUTOANTIGENS

本项目的目的是确定血小板膜的变化， 导致自身抗体介导清除活化或衰老的 血小板 老年血小板和凝血酶活化血小板均增加 膜结合免疫球蛋白（IG）水平，其有助于清除 这些细胞从血液循环。 然而，这些的多克隆性质 抗体已经排除了特定抗原的精确定义， 随着老化或活化而表现出的变化。 用正常人的淋巴细胞 个体和血小板存活率降低的患者，我将 分离Epstein巴尔病毒（EBV）转化的B细胞系，其分泌 对老化或活化血小板特异的人单克隆自身抗体。 这些单克隆自身抗体将用于鉴定和表征 血小板膜新抗原显示为血小板老化或变得 激活 我们的长期目标是确定导致免疫的事件 介导的血小板清除率，并制定延长 血小板减少相关疾病状态下的血小板存活率 生存 具体而言，我打算： 1.）的人。分离分泌单克隆抗体的人EBV转化的B细胞系 对老化或活化血小板有特异性的自身抗体。 2.）从生物化学上表征发生的血小板膜变化 这些人类单克隆抗体识别出老化或活化 自身抗体 3.）第三章表征抗原表达模式：在正常血小板 体外和体内老化，体内和体内血小板活化后， 体外和与血小板存活缩短相关的疾病状态中。

The aim of this project is to define the platelet membrane changes which lead to autoantibody mediated clearance of activated or senescent platelets. Both aged and thrombin activated platelets have increased levels of membrane bound immunoglobulin (Ig) which facilitates clerance of these cells from circulation. However, the polyclonal nature of these antibodies has precluded a precise definition of the specific antigenic changes expressed with aging or activation. Using lymphocytes from normal individuals and from patients with decreased platelet survival, I will isolate Epstein Barr Virus (EBV) transformed B cell lines which secrete human monoclonal autoantibodies specific for aged or activated platelets. These monoclonal autoantibodies will be used to identify and characterize platelet membrane neoantigens revealed as platelets age or become activated. Our long term goal is to define the events leading to immune mediated platelet clearance in man and develop strategies to prolong platelet survival in disease states associated with shortened platelet survival. Specifically I intend to: 1.) Isolate human EBV transformed B cell lines which secrete monoclonal autoantibodies specific for aged or activated platelets. 2.) Biochemically characterize the platelet membrane changes that occur with aging or activation as recognized by these human monoclonal autoantibodies. 3.) Characterize the pattern of antigen expression: during normal platelet aging in vitro and in vivo, following platelet activation in vivo and in vitro, and in disease states associated with shortened platelet survival.