Cambridge Institute for Medical Research, Cambridge, UK.
Eur J Immunol. 2009 Nov;39(11):3207-16. doi: 10.1002/eji.200939502.
To date five ULBP/RAET (UL16-binding protein, also known as retinoic acid early transcript) genes, encoded on human chromosome 6q24.2-q25.3, have been shown to encode ligands of the activating immunoreceptor NKG2D. Here, we show that a sixth gene, ULBP6/RAET1L, is a polymorphic locus that expresses a functional transcript. ULBP6 had a more restricted expression profile in cell lines and primary human tissues than other NKG2D ligands, but expression was detected in several human papillomavirus-positive cervical carcinoma cell lines and was inducible on infection with human CMV. ULBP6 bound to recombinant NKG2D as well as the human CMV immune evasion molecule UL16. By confocal microscopy we show that UL16 retains ULBP6 inside the cell, preventing it from reaching the cell surface. Expression of ULBP6 on target cells induced a significant increase in NK-cell killing. Comparison of ULBP6 with ULBP4 and ULBP5 indicated that differences in recombinant NKG2D binding correlated with differences in NK-cell activation.
迄今为止，已经在人类染色体 6q24.2-q25.3 上鉴定出了 5 个 ULBP/RAET（UL16 结合蛋白，也称为维甲酸早期转录物）基因，这些基因编码激活免疫受体 NKG2D 的配体。在这里，我们表明第六个基因 ULBP6/RAET1L 是一个多态性基因座，可表达功能性转录本。与其他 NKG2D 配体相比，ULBP6 在细胞系和原代人体组织中的表达谱更为受限，但在几种人乳头瘤病毒阳性宫颈癌细胞系中检测到表达，并可在感染人巨细胞病毒时诱导表达。ULBP6 与重组 NKG2D 以及人巨细胞病毒免疫逃逸分子 UL16 结合。通过共聚焦显微镜，我们表明 UL16 将 ULBP6 保留在细胞内，防止其到达细胞表面。靶细胞上的 ULBP6 表达可显著增加 NK 细胞的杀伤作用。与 ULBP4 和 ULBP5 的比较表明，重组 NKG2D 结合的差异与 NK 细胞激活的差异相关。
