论文题目: | Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation |
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作者: | Huang, Man Zhang, Wei Guo, Jie Wei, Xundong Phiwpan, Krung Zhang, Jianhua Zhou, Xuyu |
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刊物名称: | Sci Rep |
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年份: | 2016 |
影响因子: | 5.525 |
论文下载: | http://www.nature.com/articles/srep33612 |
摘要: | 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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