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.

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.

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 confi...

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Autores principales: Zhitao Ru, Wenjun Xiao, Anthony Pajot, Zhihua Kou, Shihui Sun, Bernard Maillere, Guangyu Zhao, David M Ojcius, Yu-Chun Lone, Yusen Zhou
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:50ca65b91901460ea095b467d06551a72021-11-18T07:26:09ZDevelopment 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.1932-620310.1371/journal.pone.0032247https://doaj.org/article/50ca65b91901460ea095b467d06551a72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22403638/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203A 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.Zhitao RuWenjun XiaoAnthony PajotZhihua KouShihui SunBernard MaillereGuangyu ZhaoDavid M OjciusYu-Chun LoneYusen ZhouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32247 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Zhitao Ru
Wenjun Xiao
Anthony Pajot
Zhihua Kou
Shihui Sun
Bernard Maillere
Guangyu Zhao
David M Ojcius
Yu-Chun Lone
Yusen Zhou
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.
description 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.
format article
author Zhitao Ru
Wenjun Xiao
Anthony Pajot
Zhihua Kou
Shihui Sun
Bernard Maillere
Guangyu Zhao
David M Ojcius
Yu-Chun Lone
Yusen Zhou
author_facet Zhitao Ru
Wenjun Xiao
Anthony Pajot
Zhihua Kou
Shihui Sun
Bernard Maillere
Guangyu Zhao
David M Ojcius
Yu-Chun Lone
Yusen Zhou
author_sort Zhitao Ru
title 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.
title_short 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_sort 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.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/50ca65b91901460ea095b467d06551a7
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