Molecular regulation of T cell activation signals by TRAF3

 描述(申请人提供)：近年来，受肿瘤坏死因子受体(TNFR)相关因子(TRAF)调控的免疫细胞受体和信号通路的数量和种类稳步增长。TRAF3最初是通过与CD40受体的联系而确定的，现已成为一种特别多功能的免疫过程调节因子。此前，TRAF3主要在B淋巴细胞、髓系细胞和非免疫细胞中进行研究。然而，最近的研究表明，TRAF3在T淋巴细胞生物学调节中也扮演着几个重要的和不同的角色，尽管这是如何发生的才刚刚开始 被拆解。这项拟议的项目关注于这一知识鸿沟，旨在满足理解TRAF3如何调节T细胞激活的关键需求。这个问题将在三个特定的目标下进行，以揭示：1)TRAF3在促进TCR信号转导中的作用。2)角色 TRAF3-CD28相互作用在调节T细胞信号中的作用；3)TRAF3在抑制1型干扰素受体(IFNAR)向T细胞信号传递中的作用。该项目的预期结果是重要的新知识，将改变对T细胞信号的基本理解，提供新的基本免疫学知识，反过来将为寻求操纵T细胞激活过程的潜在治疗应用提供信息。

 DESCRIPTION (provided by applicant): The number and variety of immune cell receptors and signaling pathways shown to be regulated by the tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) has steadily grown in recent years. TRAF3, initially identified through its association with the CD40 receptor, has emerged as an especially versatile regulator of immune processes. Previously, TRAF3 was studied primarily in B lymphocytes, myeloid cells, and non-immune cells. However, recent studies reveal that TRAF3 also plays several important and distinct roles in regulation of T lymphocyte biology, although how this occurs is only starting to be unraveled. The proposed project focuses upon this knowledge gap, and aims to fulfill a critical need to understand how TRAF3 regulates T cell activation. This question will be pursued in three Specific Aims, to uncover: 1) The role of TRAF3 in facilitating TCR signaling. 2) The role of TRAF3-CD28 interactions in regulation of T cell signaling and 3) The role of TRAF3 in restraining signaling to T cells by the type 1 interferon receptor (IFNAR). The expected outcomes of this project are important new knowledge that will revise fundamental understanding of T cell signaling, providing novel basic immunology knowledge that will in turn inform potential therapeutic applications that seek to manipulate the process of T cell activation.