Tabeta Koichi, Hoebe Kasper, Janssen Edith M, Du Xin, Georgel Philippe, Crozat Karine, Mudd Suzanne, Mann Navjiwan, Sovath Sosathya, Goode Jason, Shamel Louis, Herskovits Anat A, Portnoy Daniel A, Cooke Michael, Tarantino Lisa M, Wiltshire Tim, Steinberg Benjamin E, Grinstein Sergio, Beutler Bruce
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Nat Immunol. 2006 Feb;7(2):156-64. doi: 10.1038/ni1297. Epub 2006 Jan 15.
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.
在此，我们鉴定出了“三联D”（3D），这是一种隐性的N-乙基-N-亚硝基脲诱导的突变及表型，其中通过细胞内Toll样受体3、7和9（分别为双链RNA、单链RNA和未甲基化DNA的传感器）不会发生信号传导。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体II类呈递；它还导致对小鼠巨细胞病毒和其他微生物感染的高度易感性。通过定位鉴定，我们发现3D是Unc93b1的一个错义等位基因，该基因编码具有12个跨膜结构域的蛋白UNC-93B，这是一种在内质网中发现的高度保守分子，在哺乳动物中有多个旁系同源物。对核酸的天然反应和外源性抗原呈递均在内体中起始，因此似乎依赖于一种内质网驻留蛋白，这表明这些细胞器系统之间存在通讯。
