A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition.
A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition.
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DOI：
10.1016/j.molimm.2009.11.003
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发表时间：
2010-02
影响因子：
3.6
通讯作者：
Chuang TH
中科院分区：
文献类型：
--
作者：
Liu J;Xu C;Hsu LC;Luo Y;Xiang R;Chuang TH
Toll样受体在调节免疫抵抗微生物感染中起重要作用。Toll样受体8（TLR8）属于包括TLR7、TLR8和TLR9的亚家族。人TLR8通过识别ssRNA病毒介导抗病毒免疫，并在通过合成的小分子量配体连接后引发有效的抗病毒和抗肿瘤免疫应答。有趣的是，与人TLR8不同，小鼠TLR8在不存在聚T-寡脱氧核苷酸（polyT-ODN）的情况下对配体刺激没有响应。这种不同配体识别的分子基础仍不清楚。在本研究中，我们比较了不同物种的TLR8的激活，包括小鼠，大鼠，人，牛，猪，马，羊和猫的配体连接。只有来自啮齿动物物种的TLR 8（即，小鼠和大鼠TLR8）在没有聚T-ODN的情况下不能对配体刺激产生应答。多序列比对分析表明，这两个啮齿类TLR8缺乏一个5个氨基酸的基序，这是保守的非啮齿类物种的不同序列。该小基序位于hTLR 8胞外域的未定义区域中，紧接着LRR-14。缺失突变分析表明，该基序是必不可少的物种特异性的配体识别的hTLR8，而它不是必需的自我二聚化和细胞内定位的这种受体。
Toll-like receptors play important roles in regulating immunity against microbial infections. Toll-like receptor 8 (TLR8) belongs to a subfamily comprising TLR7, TLR8 and TLR9. Human TLR8 mediates anti-viral immunity by recognizing ssRNA viruses, and triggers potent anti-viral and antitumor immune responses upon ligation by synthetic small molecular weight ligands. Interestingly, distinct from human TLR8, mouse TLR8 was not responsive to ligand stimulation in the absence of polyT-oligodeoxynucleotides (polyT-ODN). The molecular basis for this distinct ligand recognition is still unclear. In the present study, we compared activation of TLR8 from different species including mouse, rat, human, bovine, porcine, horse, sheep, and cat by ligand ligations. Only the TLR8s from the rodent species (i.e., mouse and rat TLR8s) failed to respond to ligand stimulation in the absence of polyT-ODN. Multiple sequence alignment analysis suggested that these two rodent TLR8s lack a five-amino-acid motif that is conserved in the non-rodent species with varied sequence. This small motif is located in an undefined region of the hTLR8 ectodomain, immediately following LRR-14. Deletion mutation analysis suggested that this motif is essential for the species-specific ligand recognition of hTLR8, whereas it is not required for self-dimerization and intracellular localization of this receptor.
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