Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Structure. 2013 May 7;21(5):707-17. doi: 10.1016/j.str.2013.03.003. Epub 2013 Apr 11.
T cell activity is controlled by a combination of antigen-dependent signaling through the T cell receptor and a set of auxiliary signals delivered through antigen-independent interactions, including the recognition of the B7 family of ligands. B7-H3 is a recently identified B7 family member that is strongly overexpressed in a range of cancers and correlates with poor prognosis. We report the crystal structure of murine B7-H3 at a 3 Å resolution, which provides a model for the organization of the IgV and IgC domains within the ectodomain. We demonstrate that B7-H3 inhibits T cell proliferation and show that the FG loop of the IgV domain plays a critical role in this function. B7-H3 crystallized as an unusual dimer arising from the exchange of the G strands in the IgV domains of partner molecules. This arrangement, in combination with previous reports, highlights the dynamic nature and plasticity of the immunoglobulin fold.
T 细胞的活性受到 T 细胞受体的抗原依赖性信号和一组通过非抗原依赖性相互作用传递的辅助信号的共同控制，包括对 B7 配体家族的识别。B7-H3 是最近鉴定的 B7 家族成员，在多种癌症中过度表达，并与预后不良相关。我们报道了鼠 B7-H3 的晶体结构，分辨率为 3Å，为 IgV 和 IgC 结构域在胞外域中的构象提供了模型。我们证明 B7-H3 抑制 T 细胞增殖，并表明 IgV 结构域的 FG 环在该功能中起关键作用。B7-H3 以一种不寻常的二聚体形式结晶，这种二聚体是由配体分子的 IgV 结构域中的 G 链交换产生的。这种排列方式，结合之前的报道，突出了免疫球蛋白折叠的动态性质和可塑性。
