T CELL RECEPTOR/CD3 COMPLEX IN IMMUNOLOGIC DISEASES

免疫疾病中的 T 细胞受体/CD3 复合物

• 批准号: 3091988
• 负责人: CORNELIS P TERHORST
• 金额: $ 50.97万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-30 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3091988
• 关键词: CD3 molecule; T cell receptor; T lymphocyte; immunodeficiency; molecular pathology

The immune response combines extraordinary specificity of recognition with extremely complex control mechanisms that govern its effector mechanisms. Childhood primary immunodeficiency disorders can be viewed as "experiments of nature" in which a discrete genetic defect affects the expression and/or the structure and function of essential lymphocyte proteins and results in immune dysfunctions. A molecular or genetic definition of primary immunodeficiencies is essential for accurate diagnosis and therapy of the disorders and for better understanding of normal immune functions. In this program project we propose to study a limited set of immunologic diseases, namely childhood T cell immunodeficiency diseases and atopic dermatitis. We will use recently acquired knowledge of T cell receptor structure and T cell activation to define the immunologic defects in these diseases. In parallel we will attempt to mimic those diseases in animal models by using the powerful tools of modern genetic engineering and DNA transfer into mouse embryos. The definition of T cell immunodeficiencies and immunological skin disorders in mice will permit a better understanding of these diseases. Once the objectives have been reached, the future directions of the program lead undoubtedly toward gene therapy via bone marrow transplant. As such, the model systems described in this proposal may have a wider impact on other immunological diseases (e.g., autoimmune diseases). The prospect for generating mutations in preselected genes of the immune system not only will permit the derivation of precise animal models of human hereditary diseases but also will mark the beginning of a systematic genetic dissection of the developmental processes that play a role in the ontogeny of the immune system.

免疫反应结合了非凡的识别特异性 具有极其复杂的控制机制来控制其效应器 机制。 可以查看儿童原发性免疫缺陷病 作为“自然实验”，其中离散的遗传缺陷影响 必需淋巴细胞的表达和/或结构和功能 蛋白质并导致免疫功能障碍。 分子或遗传 原发性免疫缺陷的定义对于准确判断至关重要 疾病的诊断和治疗以及更好地了解 正常的免疫功能。 在这个计划项目中，我们建议研究 有限的免疫疾病，即儿童 T 细胞疾病 免疫缺陷疾病和特应性皮炎。 我们最近会用到 获得 T 细胞受体结构和 T 细胞激活的知识 定义这些疾病的免疫缺陷。 与此同时，我们将 尝试通过使用强大的功能在动物模型中模拟这些疾病 现代基因工程和将 DNA 转移到小鼠胚胎中的工具。 T细胞免疫缺陷和免疫性皮肤的定义 小鼠疾病将有助于更好地了解这些疾病。 目标达成后，下一步的方向 该计划无疑通向通过骨髓移植进行基因治疗。 因此，本提案中描述的模型系统可能具有更广泛的 对其他免疫疾病（例如自身免疫性疾病）的影响。 在免疫预选基因中产生突变的前景 系统不仅可以推导精确的动物模型 人类遗传性疾病也将标志着一个新时代的开始 对发挥作用的发育过程进行系统的遗传解剖 在免疫系统个体发育中的作用。