Inhibition of mouse TAP by immune evasion molecules encoded by non-murine herpesviruses.
Inhibition of mouse TAP by immune evasion molecules encoded by non-murine herpesviruses.
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非鼠疱疹病毒编码的免疫逃避分子对小鼠 TAP 的抑制
DOI：
10.1016/j.molimm.2010.12.008
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发表时间：
2010
影响因子：
3.6
通讯作者：
Wiertz E
中科院分区：
文献类型：
--
作者：
Verweij MC;Knetsch W;Quinten E;Halenius A;van Bel N;Drijfhout JW;Ressing ME;Hengel H;van Hall T;Wiertz E
疱疹病毒通过特异性干扰MHC I类（MHC I）分子的抗原呈递功能而逃脱细胞毒性T淋巴细胞的消灭。与抗原加工相关的转运蛋白（TAP）在MHC I抗原呈递途径中形成瓶颈。事实上，多种病毒，尤其是疱疹病毒，编码阻断TAP功能的分子就是一个很好的例子。这些病毒免疫球蛋白的作用通常是有效的和非常特异性的，使这些蛋白质成为研究抗原呈递的细胞生物学的有价值的工具，包括抗原加工途径的替代。然而，没有专门的TAP抑制剂被描述用于任何小鼠疱疹病毒。为了在小鼠模型中使用来自非小鼠疱疹病毒的免疫球蛋白，我们评估了四种TAP抑制剂和一种tapasin抑制剂在三种不同小鼠单倍型（H-2b、H-2d和H-2k）下的跨物种活性。四种TAP抑制剂中的两种，牛疱疹病毒1编码的UL49.5蛋白和人巨细胞病毒（HCMV）编码的US6蛋白，能有效抑制小鼠TAP。ICP47和BNLF2a分别由单纯疱疹病毒1和爱泼斯坦-巴尔病毒编码，在所有小鼠细胞中均不能抑制TAP。然而，先前的研究表明，US6不会跨越小鼠物种屏障。我们现在表明，在108位的半胱氨酸残基的取代是导致缺乏活性的原因。hcmv编码的tapasin抑制剂US3在3T3细胞上有效下调h -2分子，但在其他细胞系上没有作用。最后，我们证明了包含US6功能域的合成肽可以作为多功能TAP抑制剂被利用。总之，完整的概述了疱疹病毒编码的TAP和tapasin抑制剂在不同遗传背景的小鼠细胞中的适用性。
Herpesviruses escape elimination by cytotoxic T lymphocytes through specific interference with the antigen-presenting function of MHC class I (MHC I) molecules. The transporter associated with antigen processing (TAP) forms a bottleneck in the MHC I antigen presentation pathway. The fact that multiple viruses, especially herpesviruses, encode molecules blocking TAP function is a case in point. The action of these viral immuno evasins is usually potent and very specific, making these proteins valuable tools for studying the cell biology of antigen presentation, including alternative antigen processing pathways. Yet, no dedicated TAP inhibitor has been described for any of the mouse herpesviruses. To permit the use of immuno evasins derived from non-mouse herpesviruses in mouse models, we assessed the cross-species activity of four TAP inhibitors and one tapasin inhibitor in the context of three different mouse haplotypes, H-2b, H-2d, and H-2k. Two of the four TAP inhibitors, the bovine herpesvirus 1-encoded UL49.5 and the human cytomegalovirus (HCMV)-encoded US6 protein, potently inhibited mouse TAP. ICP47 and BNLF2a, encoded by herpes simplexvirus 1 and Epstein–Barr virus, respectively, failed to inhibit TAP in all mouse cells tested. Previous work, however, demonstrated that US6 did not cross the mouse species barrier. We now show that substitution of the cysteine residue at position 108 was responsible for this lack of activity. The HCMV-encoded tapasin inhibitor US3 efficiently downregulated H-2dmolecules on 3T3 cells, but not in other cell lines tested. Finally, we show that synthetic peptides comprising the functional domain of US6 can be exploited as a versatile TAP inhibitor. In conclusion, a complete overview is presented of the applicability of herpesvirus-encoded TAP and tapasin inhibitors in mouse cells of different genetic background.
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影响因子：
30.5
作者：
Ackerman, AL;Kyritsis, C;Cresswell, P
通讯作者：
Cresswell, P
影响 Ld 结合和组装的 Tapasin 区域1
影响因子：
4.4
作者：
H. Turnquist;S. E. Vargas;A. Reber;M. McIlhaney;Suling Li;Ping Wang;S. Sanderson;B. Gubler;P. van Endert;Joyce C. Solheim
通讯作者：
Joyce C. Solheim
影响因子：
11.4
作者：
Tomazin, R;Hill, AB;Johnson, DC
通讯作者：
Johnson, DC
影响因子：
5.4
作者：
Pande, NT;Powers, C;Früh, K
通讯作者：
Früh, K
影响因子：
5.4
作者：
Lipinska, Andrea D.;Koppers-Lalic, Danijela;Wiertz, Emmanuel J. H. J.
通讯作者：
Wiertz, Emmanuel J. H. J.