T-cell co-stimulation through CD28/CTLA4:B7-1/B7-2 axis is one of the extensively studied pathways that resulted in the discovery of several FDA-approved drugs for autoimmunity and cancer. However, many aspects of the signaling mechanism remain elusive, including oligomeric association and clustering of B7-2 on the cell surface. Here, we describe the structure of the IgV domain of B7-2 and its cryptic association into 1D arrays that appear to represent the pre-signaling state of B7-2 on the cell membrane. Super-resolution microscopy experiments on heterologous cells expressing B7-2 and B7-1 suggest, B7-2 form relatively elongated and larger clusters compared to B7-1. The sequence and structural comparison of other B7 family members, B7-1:CTLA4 and B7-2:CTLA-4 complex structures, support our view that the observed B7-2 1D zipper array is physiologically important. This observed 1D zipper-like array also provides an explanation for its clustering, and upright orientation on the cell surface, and avoidance of spurious signaling.

中文翻译：

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B7-2分子的隐秘关联及其对聚类的意义

通过 CD28/CTLA4:B7-1/B7-2 轴的 T 细胞共刺激是广泛研究的途径之一，导致发现了几种 FDA 批准的自身免疫和癌症药物。然而，信号机制的许多方面仍然难以捉摸，包括 B7-2 在细胞表面的寡聚结合和聚集。在这里，我们描述了 B7-2 的 IgV 结构域的结构及其与 1D 阵列的神秘关联，这些阵列似乎代表了 B7-2 在细胞膜上的信号前状态。对表达 B7-2 和 B7-1 的异源细胞的超分辨率显微镜实验表明，与 B7-1 相比，B7-2 形成相对拉长和更大的簇。其他 B7 家族成员的序列和结构比较，B7-1:CTLA4 和 B7-2:CTLA-4 复杂结构，支持我们的观点，即观察到的 B7-2 1D 拉链阵列在生理上很重要。这种观察到的 1D 拉链状阵列也解释了它的聚类、细胞表面的直立方向以及避免虚假信号。