The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9
The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9
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DOI：
10.1038/ni1297
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发表时间：
2006-02-01
影响因子：
30.5
通讯作者：
Beutler, B
中科院分区：
文献类型：
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作者：
Tabeta, K;Hoebe, K;Beutler, B
在这里，我们已经确定了'三重D'（3d），隐性N-乙基-N-亚硝基脲诱导的突变和表型，其中没有信号发生通过细胞内Toll样受体3，7和9（传感器的双链RNA，单链RNA和未甲基化的DNA，分别）。3d突变还阻止了交叉呈递，并减少了外源性抗原的主要组织相容性复合物II类呈递;它还引起了对小鼠巨细胞病毒和其他微生物感染的过敏性。通过位置鉴定，我们发现3d是Unc 93 b1的错义等位基因，Unc 93 b1编码12-跨膜蛋白E12 - 93 B，E12 - 93 B是一种在哺乳动物内质网中发现的高度保守分子，具有多种旁系同源物。因此，对核酸的先天反应和外源抗原提呈（均在核内体中启动）似乎取决于内质网驻留蛋白，这表明这些细胞器系统之间存在通讯。
Here we have identified 'triple D' (3d), a recessive N-ethyl-N-nitrosourea-induced mutation and phenotype in which no signaling occurs via the intracellular Toll-like receptors 3, 7 and 9 (sensors for double-stranded RNA, single-stranded RNA and unmethylated DNA, respectively). The 3d mutation also prevented cross-presentation and diminished major histocompatibility complex class II presentation of exogenous antigen; it also caused hypersusceptibility to infection by mouse cytomegalovirus and other microbes. By positional identification, we found 3d to be a missense allele of Unc93b1, which encodes the 12-membrane-spanning protein UNC-93B, a highly conserved molecule found in the endoplasmic reticulum with multiple paralogs in mammals. Innate responses to nucleic acids and exogenous antigen presentation, which both initiate in endosomes, thus seem to depend on an endoplasmic reticulum-resident protein, which suggests communication between these organellar systems.