title: Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation.
abstract: The rapid occurrence of emerging infectious diseases demonstrates an urgent need for a new preclinical experimental model that reliably replicates human immune responses. Here, a new homozygous humanized human leukocyte antigen (HLA)-A11/DR1 transgenic mouse (HLA-A11(+/+)/DR01(+/+)/H-2-β2m(-/-)/IAβ(-/-)) was generated by crossing HLA-A11 transgenic (Tg) mice with HLA-A2(+/+)/DR01(+/+)/H-2-β2m(-/-)/IAβ(-/-) mice. The HLA-A11-restricted immune response of this mouse model was then examined. HLA-A11 Tg mice expressing a chimeric major histocompatibility complex (MHC) molecule comprising the α1, α2, and β2m domains of human HLA-A11 and the α3 transmembrane and cytoplasmic domains of murine H-2D(b) were generated. The correct integration of HLA-A11 and HLA-DR1 into the genome of the HLA-A11/DR1 Tg mice (which lacked the expression of endogenous H-2-I/II molecules) was then confirmed. Immunizing mice with a recombinant HBV vaccine or a recombinant HIV-1 protein resulted in the generation of IFN-γ-producing cytotoxic T lymphocyte (CTL) and antigen-specific antibodies. The HLA-A11-restricted CTL response was directed at HLA immunodominant epitopes. These mice represent a versatile animal model for studying the immunogenicity of HLA CTL epitopes in the absence of a murine MHC response. The established animal model will also be useful for evaluating and optimizing T cell-based vaccines and for studying differences in antigen processing between mice and humans.
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.|b INSERM U1197 (ex U1014), University of Paris-Sud, Hospital Paul Brousse , Villejuif , France.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: c Wenzhou Medical University , Zhejiang , China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Gao
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Kou
authors.affiliation: b INSERM U1197 (ex U1014), University of Paris-Sud, Hospital Paul Brousse , Villejuif , France.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Lone
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing , China.|c Wenzhou Medical University , Zhejiang , China.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D003433:Crosses, Genetic; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D015483:HIV Antibodies / Q000097:blood; D059870:HLA-A11 Antigen / Q000235:genetics*; D015798:HLA-DR1 Antigen / Q000235:genetics*; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006720:Homozygote; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008822:Mice, Transgenic; D023421:Models, Animal; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D059870:HLA-A11 Antigen; D015798:HLA-DR1 Antigen; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D007371:Interferon-gamma
keywords: HLA; HLA-A11/DR1 transgenic mice; MHC; MHC-restricted epitopes; Vaccine