ISOLATION OF A HUMAN HOMOLOGUE OF THE MURINE LY-6 SYSTEM

小鼠Ly-6基因座编码一组细胞表面分子 表达于各种淋巴系、髓系等多种细胞类型。 这些Ly-6编码分子中至少有两个，Ly-6E.1和TAP， 并参与T淋巴细胞的活化。其中一种的cdna LY-6蛋白是最近分离到的一种蛋白，并对其进行了研究 证实Ly-6是一个复杂的多基因家族。我们建议 利用小鼠的cDNA分离和鉴定人 小鼠Ly-6系统的同源物。人类的存在 与Ly-6同源的序列将通过探针确定 人基因组DNA与小鼠Ly-6的Southern杂交 CDNA.表达Ly-6同源基因的细胞将是 用Ly-6基因进行Northern杂交鉴定。Cdna 来自表达Ly-6相关消息的细胞的文库将 用Ly-6探针和同源克隆进行筛选 与世隔绝。这些人类cDNAs的特征是 限制分析，并将进行测序。多肽将是 根据推导的氨基酸序列和Will合成的 用来产生特定的抗体。全长cDNA的遗嘱 在表达载体中表达，分离的蛋白将 用于结构研究和生成特定的 抗体。这些cDNA和抗体将被用于 人类Ly-6系统的结构及其作用的研究 在细胞激活中起作用。 这项工作的主要长期目标是确定和 表征参与转导过程的分子 细胞外信息和细胞激活。它已经变成了 最近明确了细胞的附着功能或控制 激活分子可能是某些或许多人类的病因 恶性肿瘤。此外，活化的淋巴细胞是一种重要的 治疗某些人类恶性肿瘤的新方法。 阐明人类Ly-6系统应该进一步推动我们的 了解癌症并协助其治疗。

The murine Ly-6 locus encodes a group of cell surface molecules expressed on a variety of lymphoid, myeloid and other cell types. At least two of these Ly-6 encoded molecules, Ly-6E.1 and TAP, and involved in T lymphocytes activation. A cDNA for one of the Ly-6 proteins was isolated recently and studies with this cDNA confirm that Ly-6 is a complex multigene family. We propose to use the murine cDNA to isolate and characterize a human homologue of the murine Ly-6 system. The existence of human sequences homologous to Ly-6 will be determined by probing Southern blots of human genomic DNA with the murine Ly-6 cDNA. Cells expressing mRNA homologous to Ly-6 will be identified by probing Northern blots with the Ly-6 cDNA. cDNA libraries from cells expressing Ly-6 related messages will be screened with the Ly-6 probe and homologous clones will be isolated. These human cDNA's will be characterized by restriction analysis and will be sequenced. Peptides will be synthesized based on the deduced amino acid sequences and will be used to generate specific antibodies. Full length cDNA's will be expressed in expression vectors and the isolated proteins will be used for structural studies and for the generation of specific antibodies. These cDNA's and antibodies will be utilized for studying the structure of the human Ly-6 system and the role it plays in cellular activation. The major long-term objective of this work is to identify and characterize molecules involved in the process of transducing extracellular messages and cellular activation. It has become clear recently that adherent function or control of cellular activation molecules may be an etiology for some or many human malignancies. Moreover, activated lymphocytes are an important new modality in the treatment of some human malignancies. Elucidating the human Ly-6 system should further our understanding of cancer and aid in its treatment.