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: 7151461
• 负责人: Wendy L. Havran
• 金额: $ 45.13万
• 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/7151461
• 关键词: Adhesions; Adult; Affect; Antigen-Presenting Cells; Antigens; Apoptotic; Autoantigens; Binding; CD28 gene; CD8B1 gene; Cell Communication; Cell physiology; Cells; Condition; Data; Disease; Epithelial; Epithelial Cells; Event; Family; Homeostasis; Immune response; In Vitro; Integrins; Intestines; Knock-out; Ligands; Ligation; Localized; Lymphoid; Lymphoid Cell; Mediating; Mitogens; Mus; Numbers; Personal Satisfaction; Play; Population; Production; Rest; Role; Signal Transduction; Site; Skin; Surface; T-Cell Proliferation; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Tissues; Wound Healing; cytokine; junctional adhesion molecule; keratinocyte; member; novel; programs; prototype; receptor; repaired; research study; response

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（由申请人提供）：T细胞携带不变性？？T细胞抗原受体（TCR）定位于成年小鼠的不同上皮部位，在那里它们与非经典抗原呈递细胞（如上皮细胞）相互作用。其中很多？？T细胞群不表达传统的共刺激分子，如CD28，这表明它们可能依赖于通过新型受体-配体相互作用传递的信号。我们已经确定AMICA是连接粘附分子家族的成员，作为上皮细胞的共刺激分子。T细胞。美国对所有人都表达了自己的看法？？T细胞和体外有丝分裂原激活导致表面表达上调。在淋巴样细胞中，AMICA优先由？？T细胞虽然是CD8+的一个小亚群？T细胞活化后也表达AMICA。通过AMICA传递的信号共同刺激皮肤和肠道？T细胞增殖和细胞因子释放，但没有任何激活？T细胞还是淋巴细胞？T细胞。我们将验证AMICA通过上皮细胞表达的假设。T细胞与受损上皮细胞上表达的配体结合这种新型受体-配体对之间的相互作用向？？T细胞是参与局部免疫反应包括组织稳态和修复的关键。总之，这些研究应该确定AMICA在上皮细胞的激活和功能中的作用。T细胞，并可能适用于操作？？上皮疾病中的T细胞反应。