PLATELET AUTONANTIGENS

这个项目的目的是定义血小板膜的变化 导致自身抗体介导的活化或衰老的清除 血小板。老化的和凝血酶激活的血小板都增加了 促进血管硬化的膜结合免疫球蛋白(Ig)水平 这些细胞来自血液循环。然而，这些基因的多克隆性质 抗体排除了对特定抗原的准确定义 随着年龄的增长或激活而表现出的变化。使用正常人的淋巴细胞 从个人和血小板存活率下降的患者来看，我会 EB病毒转化的B细胞株的分离 针对老化或活化的血小板的人单克隆自身抗体。 这些单抗将被用来鉴定和鉴定 血小板膜新抗原显示为血小板老化或变成 激活了。我们的长期目标是定义导致免疫的事件 人类体内介导的血小板清除及其延长策略的研究 与血小板缩短相关的疾病状态下的血小板存活 生死存亡。 具体地说，我打算： 1)分离分泌单抗的人EB病毒转化B细胞系 针对老化或激活的血小板的自身抗体。 2.)血小板膜发生变化的生化特征 与这些人类单抗所识别的老化或激活 自身抗体。 3.)抗原表达模式的特征：在正常血小板期间 体内和体内血小板活化后的体外和体内老化 在体外，以及在与血小板存活时间缩短相关的疾病状态下。

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.