RECOGNITION OF LEUKEMIA ANTIGEN BY ANTI-VIRAL CTL'S

我们建议确定抗病毒CTL识别或 小鼠不能识别白血病病毒细胞表面抗原 系统。特别是，我们计划研究为什么正常细胞来自 携带Akv-1小鼠白血病前病毒的AKXL小鼠是 被C57B1/6抗AKR/Gross病毒CTL识别，而细胞 从其他携带高度相关Akv-4的AKXL小鼠中分离出来的 这种抗病毒CTL不能识别前病毒。 同事们使用了标准的免疫学技术，包括 CTL识别和诱导试验与抗病毒单抗 抗体识别测试清楚地表明了 病毒抗原gp70在CTL识别过程中的作用。至 进一步研究CTL识别病毒表位的表达 在此建议通过限制映射来克隆和比较 AKV-1和AkV-4前病毒DNA基因座。细胞表面病毒 由这些前病毒表达并被CTL识别的抗原将 然后通过转染重组人进行研究和比较 前病毒亚克隆为成纤维细胞或淋巴母细胞系。 将转基因细胞在G418选择性培养基中培养后， 病毒抗原的表达将通过细胞荧光照相进行检测 用抗病毒单抗和CTL功能 化验。通过这些手段，我们可以更好地定义病毒成分 对于CTL识别和诱导是必要的，并且更好 了解由以下因素导致的肿瘤建立的促进 这些过程的失败。

We propose to identify ways in which anti-viral CTL recognize or fail to recognize leukemia virus cell surface antigen in the murine system. In particular, we plan to study why normal cells from AKXL mice, which carry the Akv-1 murine leukemia provirus, are recognized by C57B1/6 anti-AKR/Gross virus CTL, whereas cells from other AKXL mice which carry the highly related Akv-4 provirus, are not recognized by such antiviral CTL's. Green and coworkers have used standard immunological techniques including CTL recognition and induction assays and antiviral monoclonal antibody recognition assays that clearly indicate the importance of the viral antigen gp70 in the CTL recognition process. To further study viral epitope expression for recognition by CTL, I propose here to clone and compare by restriction mapping the Akv-1 and Akv-4 proviral DNA loci. The cell surface viral antigens expressed by these proviruses and recognized by CTL will then be studied and compared by transfecting recombinant proviral subclones into fibroblast or lymphoblastoid cell lines. After culturing the transfected cells in G418 selective medium, viral antigen expression will be assayed for by cytofluorography using antiviral monoclonal antibodies and by CTL functional assays. By these means, we can better define the viral elements necessary for CTL recognition and induction and better understand the promotion of tumor establishment resulting from the failure of these processes.