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建立人源 HLA-A2.1/DP4 转基因小鼠模型，并利用该模型对 HBV 包膜蛋白中 HLA-DP4 限制性表位进行定位。

Development of a humanized HLA-A2.1/DP4 transgenic mouse model and the use of this model to map HLA-DP4-restricted epitopes of HBV envelope protein.

机构信息

State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

出版信息

PLoS One. 2012;7(3):e32247. doi: 10.1371/journal.pone.0032247. Epub 2012 Mar 5.

DOI:10.1371/journal.pone.0032247
PMID:22403638
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3293898/
Abstract

A new homozygous humanized transgenic mouse strain, HLA-A2.1(+/+)HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAβ(-/-)β2m(-/-) (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2(+/+)β2m(-/-) (A2) mouse and our previously created HLA-DP4(+/+) hCD4(+/+)mCD4(-/-)IAβ(-/-) (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans.

摘要

一种新的纯合人源化转基因小鼠品系 HLA-A2.1(+/+)HLA-DP4(+/+)hCD4(+/+)mCD4(-/-)IAβ(-/-)β2m(-/-)（HLA-A2/DP4），是通过杂交先前鉴定的 HLA-A2(+/+)β2m(-/-)（A2）小鼠和我们之前创建的 HLA-DP4(+/+)hCD4(+/+)mCD4(-/-)IAβ(-/-)（DP4）小鼠获得的。我们证实，来自亲本 A2 和 DP4 小鼠的转基因（HLA-A2、HLA-DP4、hCD4）在 HLA-A2/DP4 小鼠中是有功能的。在用乙型肝炎 DNA 疫苗免疫 HLA-A2/DP4 小鼠后，观察到乙型肝炎病毒特异性抗体、HLA-A2 限制性和 HLA-DP4 限制性反应与自然感染人类的反应相似。因此，本研究表明 HLA-A2/DP4 转基因小鼠能够忠实地模拟人类细胞反应。此外，我们报道了从 HBsAg 中鉴定出的四个新的 HLA-DP4 限制性表位，这些表位在接种疫苗的 HLA-A2/DP4 小鼠和 HLA-DP4 阳性的人类个体中都被识别。HLA-A2/DP4 转基因小鼠模型是一种很有前途的携带超过四分之一人类人群等位基因的临床前动物模型。该模型将有助于鉴定新的 HLA-A2 和 HLA-DP4 限制性表位以及疫苗的开发，以及对人类感染中 HLA-DP4 限制性反应的表征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/21fca73f78ee/pone.0032247.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/a9e683a30ad6/pone.0032247.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/c7eb90a43fc9/pone.0032247.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/c4ca84c75539/pone.0032247.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/a42f857a5cdd/pone.0032247.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/21fca73f78ee/pone.0032247.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/a9e683a30ad6/pone.0032247.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/c7eb90a43fc9/pone.0032247.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/c4ca84c75539/pone.0032247.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/a42f857a5cdd/pone.0032247.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcae/3293898/21fca73f78ee/pone.0032247.g005.jpg

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