FUNCTIONAL CHARACTERIZATION OF CD69

描述（改编自研究者摘要）：免疫系统 由特定的细胞间相互作用调节， 通过一系列精心设计的细胞表面受体虽然身份 许多细胞表面受体的机制是已知的， 它们对免疫反应的影响在大多数 实例.在自身免疫性疾病中尤其如此， 不能正确调节免疫反应会导致病理性的 状态在涉及正常的细胞表面受体，以及 是CD69。CD69表达于细胞表面， 所有造血细胞系的激活细胞，而不是静止细胞。它 已经被证明参与了各种各样的生物过程， 包括胸腺细胞的阳性选择， 单核细胞释放促炎细胞因子，T细胞共刺激 刺激.尽管有大量证据表明， CD69对免疫系统发育和功能的重要性， 关于CD69是如何调节的， 功能协调发展的非常基本的问题，如CD69信号的机制 转导及其同源配体的性质，以及更多 全球性问题，如它在建立有效的免疫反应中的作用， 和传播慢性病理状态，仍然没有答案。广泛 大量证据表明，CD69在两种疾病中起着重要作用。 免疫系统、胸腺细胞发育和T细胞 激活，也是自身免疫性疾病中免疫功能障碍的区域。 疾病然而，在评估CD69在自身免疫性疾病中的作用之前， 可发疾病，详细分析其在正常情况下的作用 免疫系统的发育和功能必须进行。的 本提案中描述的实验将解决基本问题 关于CD69在胸腺细胞阳性选择中的作用， 以及CD69传递细胞内信号的机制。我们 还将识别和表征细胞表面分子， 单核细胞作为CD69受体。了解这些信息 将允许详细分析CD69在启动中的作用， 自身免疫性疾病的传播。

DESCRIPTION (Adapted from Investigator's Abstract): The, immune system is regulated by specific cell-cell interactions that are mediated through an elaborate array of cell-surface receptors. While the identity of many of the cell-surface receptors is known, the mechanisms by which they exert their influence on immune responses remains obscure in most instances. This is especially true in autoimmune diseases, where the failure to regulate immune responses properly results in a pathological state. Among the cell surface receptors implicated in normal, as well as inflammatory, responses, is CD69. CD69 is expressed on the surface of activated, but not resting, cells of all hematopoietic lineages. It has been shown to be involved in a wide variety of biological processes, including the positive selection of thymocytes, induction of proinflammatory cytokine release from monocytes, and T cell co- stimulation. In spite of the overwhelming evidence demonstrating the importance of CD69 to the development and function of the immune system, there is very little known as to how CD69 is regulated or how it functions. Very basic issues, such as the mechanism of CD69 signal transduction and the nature of its cognate ligand, as well as more global issues such as its role in mounting a competent immune response and propagating a chronic pathological state, remain unanswered. A wide body of evidence suggests that CD69 plays an important role in two aspects of the immune system, thymocyte development and T cell activation, that are also areas of immune dysfunction in autoimmune disease. However, before an assessment of CD69's role in autoimmune disease can be made, a detailed analysis of its role in the normal development and function of the immune system must be performed. The experiments described in this proposal will address basic questions concerning the role of CD69 in the positive selection of thymocytes, as well as the mechanism by which CD69 transmits intracellular signals. We will also identify and characterize the cell surface molecule on monocytes that serves as the CD69 receptor. Knowing this information will allow a detailed analysis of the role of CD69 in the initiation and propagation of autoimmune disease to be initiated.