AMICA: A New Costimulatory Molecule GammaDelta T Cells

AMICA：一种新的共刺激分子 GammaDelta T 细胞

• 批准号: 7033532
• 负责人: Wendy L. Havran
• 金额: $ 46.48万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033532
• 关键词: AMICA; New; Costimulatory; Molecule; GammaDelta

DESCRIPTION (provided by applicant): T cells bearing invariant ?? T cell antigen receptors (TCR) localize to distinct epithelial sites in the adult mouse where they interact with non-classical antigen presenting cells such as epithelial cells. Many of these ?? T cell populations do not express traditional costimulatory molecules such as CD28 suggesting that they may rely on signals delivered through novel receptor-ligand interactions. We have identified AMICA, a member of the junctional adhesion molecule family, as a costimulatory molecule for epithelial ?? T cells. AMICA is expressed on all ?? T cells and in vitro mitogen activation leads to upregulated surface expression. Among lymphoid cells, AMICA is preferentially expressed by ?? T cells although a small subpopulation of CD8+ ?? T cells also express AMICA after activation. Signals delivered through AMICA costimulate skin and intestinal ?? T cell proliferation and cytokine release but not activation of any ?? T cells or lymphoid ?? T cells. We will test the hypothesis that AMICA expressed by epithelial ?? T cells binds to a ligand expressed on damaged epithelial cells and that interaction between this novel receptor-ligand pair delivers costimulatory signals to the ?? T cell that are critical for participation in local immune responses including tissue homeostasis and repair. Together these studies should determine the roles of AMICA in the activation and function of epithelial ?? T cells and may be applicable for manipulation of ?? T cell responses in epithelial disorders.

描述(申请人提供)：T细胞具有不变性？？T细胞抗原受体(TCR)定位于成年小鼠不同的上皮部位，在那里它们与非经典的抗原提呈细胞如上皮细胞相互作用。很多这样的东西？？T细胞群体不表达CD28等传统的共刺激分子，这表明它们可能依赖于通过新颖的受体-配体相互作用传递的信号。我们已经确定AMICA是连接黏附分子家族的成员，是上皮细胞的共刺激分子。T细胞。阿米卡在所有人身上都有表达吗？？T细胞和体外丝裂原激活导致表面表达上调。在淋巴样细胞中，AMICA优先表达为？？T细胞虽然只有一小部分CD8+？？T细胞活化后也表达AMICA。通过Amica共刺激皮肤和肠道传递的信号？？T细胞的增殖和细胞因子的释放，但不激活任何？？T细胞还是淋巴样细胞？？T细胞。我们将检验阿米卡由上皮细胞表达的假说？？T细胞与受损上皮细胞上表达的一种配体结合，这种新型受体-配体对之间的相互作用将共刺激信号传递给？？T细胞是参与局部免疫反应的关键细胞，包括组织动态平衡和修复。总之，这些研究应该确定AMICA在上皮细胞激活和功能中的作用？？T细胞，可能适用于操纵？上皮性疾病中的T细胞反应。