AMICA: A New Costimulatory Molecule GammaDelta T Cells

携带不变Y5 T细胞抗原受体(TCR)的T细胞定位于不同的上皮部位。 成年小鼠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 细胞。这些Y8 T细胞群中的许多不表达传统的共刺激分子 例如CD28，表明它们可能依赖于通过新的受体-配体传递的信号 互动。我们已经鉴定出AmigA是连接黏附分子家族的成员， 作为上皮性Y8 T细胞的共刺激分子。AMIGA在所有Y5 T细胞上均有表达 在体外，丝裂原激活会导致表面表达上调。在淋巴样细胞中， 虽然有一小部分CD8+AP T细胞，但Y8 T细胞优先表达AMIGA 激活后的细胞也表达AmIGA。通过Amiga共刺激皮肤传递的信号 和肠道Y5 T细胞增殖和细胞因子的释放，但不激活任何AP T细胞或 淋巴样Y5 T细胞。我们将检验上皮性Y8 T细胞表达AmIgA的假设 与受损上皮细胞上表达的配体结合，并与这一新的 受体-配体对向y8T细胞传递共刺激信号，这些信号对 参与局部免疫反应，包括组织动态平衡和修复。把这些放在一起 研究应确定AmigA在上皮性Y8 T激活和功能中的作用 细胞，并可能适用于操纵上皮病的Y8 T细胞反应。

T cells bearing invariant y5 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 y8 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 AMIGA, a member of the junctional adhesion molecule family, as a costimulatory molecule for epithelial y8 T cells. AMIGA is expressed on all y5 T cells and in vitro mitogen activation leads to upregulated surface expression. Among lymphoid cells, AMIGA is preferentially expressed by y8 T cells although a small subpopulation of CD8+ ap T cells also express AMIGA after activation. Signals delivered through AMIGA costimulate skin and intestinal y5 T cell proliferation and cytokine release but not activation of any ap T cells or lymphoid y5 T cells. We will test the hypothesis that AMIGA expressed by epithelial y8 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 y8T cell that are critical for participation in local immune responses including tissue homeostasis and repair. Together these studies should determine the roles of AMIGA in the activation and function of epithelial y8 T cells and may be applicable for manipulation of y8 T cell responses in epithelial disorders.