Molecular regulation of T cell activation signals by TRAF3

 描述（由申请人提供）：近年来，受肿瘤坏死因子受体（TNFR）相关因子（TRAFs）调节的免疫细胞受体和信号通路的数量和种类稳步增长。TRAF 3最初通过其与CD 40受体的结合而被鉴定，现已成为免疫过程的特别通用的调节剂。以前，TRAF 3主要在B淋巴细胞、骨髓细胞和非免疫细胞中进行研究。然而，最近的研究表明，TRAF 3在调节T淋巴细胞生物学中也起着几个重要而独特的作用，尽管这一作用的发生方式才刚刚开始 被解开拟议的项目侧重于这一知识差距，旨在满足理解TRAF 3如何调节T细胞活化的关键需求。这个问题将在三个具体目标中进行，以揭示：1）TRAF 3在促进TCR信号传导中的作用。2)的作用 TRAF 3-CD 28相互作用在调节T细胞信号传导中的作用和3）TRAF 3在抑制1型干扰素受体（IFNAR）向T细胞的信号传导中的作用。该项目的预期成果是重要的新知识，将修订对T细胞信号传导的基本理解，提供新的基础免疫学知识，从而为寻求操纵T细胞活化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.