STRUCTURAL BASIS OF CD59 AND CD58 SIGNALING TO T-CELLS

描述（改编自研究者摘要）：相互作用 T淋巴细胞和抗原呈递细胞之间的粘附 这些分子也是细胞活化的调节因子。 最近，研究人员已经表明，CD 59抗原是第二个 除了公认的相互作用外， CD58（LFA-3）。 这些细胞表面抗原之间的相互作用 对免疫调节非常重要， 理解粘附分子相互作用的范例。 CD 59是 也是补体膜形成的重要调节剂 攻击复合体 在此过程中重要因素的定义 相互作用最初将通过分子研究来完成。 研究中心- 定向诱变将在编码CD 59 和CD 58抗原。 将使用单克隆抗体筛选突变体。 抗体，粘附测定和补体功能， CD59。 随后，将对这些抗原的免疫原性进行评估。 在转染到几种抗原呈递来源中后检查 细胞重组蛋白将由CHO转染子或 杆状病毒表达系统，并用于测定三种 空间结构 这些抗原以及MHC II类抗原 可能有助于内皮细胞的免疫原性。 的 CD 58、CD 59基因转染猪血管内皮细胞免疫原性研究 和/或人MHC II类的免疫原性将在体外进行初步评估。 这些 转染的细胞也将用于确定猪是否 细胞可能是异种移植到人类的潜在来源。 一种模型鼠系统，其中SCID小鼠的免疫系统已被免疫抑制剂抑制。 将采用人类细胞重建。 的免疫原性 修饰的猪内皮细胞的性质将在 合成血管网络的介绍。 这种方法还应 提供对免疫介导的损伤的深入了解。

DESCRIPTION (Adapted from the investigator's abstract):Interactions between T lymphocytes and antigen presenting cells involve adhesion molecules that are also implicated as regulators of cell activation. Recently, the investigators have shown that the CD59 antigen is a second ligand for CD2 on T cells in addition to the well recognized interaction with CD58 (LFA-3). The interactions among these cell surface antigens are very central to immune regulation and will likely form the first paradigm for understanding adhesion molecule interactions. The CD59 is also an important regulator of the formation of the complement membrane attack complex. Definition of the significant factors in this interaction will be accomplished initially with molecular studies. Site- directed mutagenesis will be performed on cDNAs encoding both the CD59 and CD58 antigens. The mutants will be screened using monoclonal antibodies, adhesion assays and for complement function in the case of CD59. Subsequently, the immunogenicity of these antigens will be examined after transfection into several sources of antigen presenting cells. Recombinant protein will be generated from CHO transfectants or baculovirus expression systems and used for determination of the three dimensional structure. These antigens as well as MHC class II antigens may contribute to the immunogenicity of endothelial cells. The immunogenicity of porcine endothelial cells transfected with CD58, CD59 and/or human MHC class II will be initially evaluated in vitro. These transfected cells will also be utilized to determine whether porcine cells could be a potential source for xenotransplantation into human. A model murine system in which the immune system of SCID mice has been reconstructed with human cells will be employed. The immunogenic properties of modified porcine endothelial cells will be evlauated after introduction in synthetic vascular networks. This approach should also provide insight into immune-mediated injury.