Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation.
Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation.
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用于研究 HLA I 类抗原呈递的改良转基因小鼠模型
DOI：
10.1038/srep33612
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发表时间：
2016-09-16
影响因子：
4.6
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Huang M;Zhang W;Guo J;Wei X;Phiwpan K;Zhang J;Zhou X
在过去的二十年中，HLA-I类（HLA-I）转基因小鼠已被证明是研究人类MHC相关免疫反应的有用模型。然而，人类和小鼠之间的加工和呈递机制的差异可能对HLA-I限制性抗原呈递有深远的影响。在这项研究中，我们建立了一种新的人TAP-LMP（hTAP-LMP）基因簇转基因小鼠模型，携带完整的人TAP复合物和两个人免疫蛋白酶体LMP亚基，PSMB 8/PSMB 9。通过将hTAP-LMP品系与不同的HLA-I转基因小鼠杂交，我们发现人HLA-I分子的表达水平，特别是A3超型成员（例如，A11和A33）在相应的HLA-I/hTAP-LMP转基因小鼠中显著增强。此外，我们发现人源化加工和呈递机制增加了HLA-A11限制性表位的抗原呈递，并促进了HLA-A11/hTAP-LMP小鼠中乙型肝炎病毒（HBV）感染的快速减少。总之，我们的研究强调HLA-I/hTAP-LMP小鼠是研究HLA-I分子的抗原呈递及其相关CTL应答的改进模型。
HLA class I (HLA-I) transgenic mice have proven to be useful models for studying human MHC-related immune responses over the last two decades. However, differences in the processing and presentation machinery between humans and mice may have profound effects on HLA-I restricted antigen presentation. In this study, we generated a novel human TAP-LMP (hTAP-LMP) gene cluster transgenic mouse model carrying an intact human TAP complex and two human immunoproteasome LMP subunits, PSMB8/PSMB9. By crossing the hTAP-LMP strain with different HLA-I transgenic mice, we found that the expression levels of human HLA-I molecules, especially the A3 supertype members (e.g., A11 and A33), were remarkably enhanced in corresponding HLA-I/hTAP-LMP transgenic mice. Moreover, we found that humanized processing and presentation machinery increased antigen presentation of HLA-A11-restricted epitopes and promoted the rapid reduction of hepatitis B virus (HBV) infection in HLA-A11/hTAP-LMP mice. Together, our study highlights that HLA-I/hTAP-LMP mice are an improved model for studying antigen presentation of HLA-I molecules and their related CTL responses.
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影响因子：
168.9
作者：
Moins-Teisserenc, HT;Gadola, SD;Cerundolo, V
通讯作者：
Cerundolo, V
影响因子：
64.8
作者：
GOMARD, E;BEGUE, B;LEVY, JP
通讯作者：
LEVY, JP
影响因子：
3.7
作者：
Ménager J;Ebstein F;Oger R;Hulin P;Nedellec S;Duverger E;Lehmann A;Kloetzel PM;Jotereau F;Guilloux Y
通讯作者：
Guilloux Y
DOI：
10.1016/j.bbrc.2009.12.100
发表时间：
2010-01-15
影响因子：
3.1
作者：
Matsui, Masanori;Kohyama, Shunsuke;Uchida, Tetsuya
通讯作者：
Uchida, Tetsuya
影响因子：
56.9
作者：
DELASALLE, H;HANAU, D;TONGIO, MM
通讯作者：
TONGIO, MM