Regulation of Immune Responses by SRCR Proteins

SRCR 蛋白对免疫反应的调节

• 批准号: 6421528
• 负责人: NIGEL Patrick KILLEEN
• 金额: $ 29.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6421528
• 关键词: CD antigens; CD5 molecule; Mycoplasma; T cell receptor; T lymphocyte; biological signal transduction; cell differentiation; experimental allergic encephalomyelitis; genetically modified animals; immunoregulation; laboratory mouse; leukocyte activation /transformation

DESCRIPTION (provided by applicant): T cell CD5 and CD6 transmembrane glycoproteins are structurally related to one another and are encoded by genes that are closely linked in the genome. Absence of CD5 in mice confers hyperresponsiveness on thymocytes and T cells to signaling through their antigen receptors. One of the goals of the research proposed in this application is to determine the mechanism of this negative regulation. For this purpose, we will use an in vitro assay that informs on the capacity of mutant CD5 molecules to inhibit T cell receptor signaling. The experiments will attempt to determine which parts of the CD5 molecule are necessary for the negative regulatory effect, and they will also identify the interacting proteins that relay the inhibition. Related experiments will address the immunoregulatory roles of the CD6 molecule and will attempt to determine how alternative splicing of the RNA encoding CD6 might affect its function at different stages of I cell development. Using mouse mutants that lack expression of CD5, CD6 or both molecules, we will attempt to determine the functions of the molecules in vivo. These experiments will involve the analysis of I cell receptor transgenic mice, and also model autoimmune and infectious systems. Preliminary data suggest that CD5 and CD6 influence the outcome of thymocyte development, the course of experimental allergic encephalomyelitis and the host response to bacterial infection. Through these in vivo experiments, we hope to understand the significance of the novel regulatory roles performed by CD5 and CD6 during autoreactive and pathogen-directed immune responses. Such an understanding may eventually lead to the development of therapeutic approaches that specifically target these molecules to regulate deleterious immune responses.

描述（由申请人提供）：T细胞CD5和CD6跨膜 糖蛋白在结构上相互关联，并由基因编码 在基因组中密切相关。小鼠中缺乏CD5 通过其胸腺细胞和T细胞的过度反应通过其信号 抗原受体。这项研究的目标之一 应用是确定这种负调节的机制。为了这 目的，我们将使用一个体外测定法，以告知突变体的能力 CD5分子抑制T细胞受体信号传导。实验会 尝试确定CD5分子的哪些部分对于 负调节效应，他们还将确定相互作用 中继抑制作用的蛋白质。相关实验将解决 CD6分子的免疫调节作用，将尝试确定 编码CD6的RNA的替代剪接可能会影响其功能 I细胞开发的不同阶段。使用缺乏的小鼠突变体 CD5，CD6或两个分子的表达，我们将尝试确定 分子在体内的功能。这些实验将涉及分析 I细胞受体转基因小鼠的自身免疫性和感染性 系统。初步数据表明，CD5和CD6影响 胸腺细胞发育，实验性过敏性脑脊髓炎的过程 以及对细菌感染的宿主反应。通过这些体内 实验，我们希望了解新型调节的重要性 CD5和CD6在自动反应性和病原体指导的免疫中执行的角色 回答。这样的理解最终可能导致 专门针对这些分子以调节的治疗方法 有害免疫反应。