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- Title
Development of a Humanized HLA-A2.1/DP4 Transgenic Mouse Model and the Use of This Model to Map HLADP4- Restricted Epitopes of HBV Envelope Protein.
- Authors
Zhitao Ru; Wenjun Xiao; Pajot, Anthony; Zhihua Kou; Shihui Sun; Maillere, Bernard; Guangyu Zhao; Ojcius, David M.; Yu-chun Lone; Yusen Zhou
- 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 HLADP4+/+ 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 HLAA2/ 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.
- Subjects
HEPATITIS B virus; TRANSGENIC mice; EPITOPES; PROTEINS; DNA; ALLELES
- Publication
PLoS ONE, 2012, Vol 7, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0032247