Generation of human MHC (HLA-A11/DR1) transgenic mice for vaccine evaluation.
Hum Vaccin Immunother
; 12(3): 829-36, 2016 03 03.
Article
en En
| MEDLINE
| ID: mdl-26479036
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-ß2m(-/-)/IAß(-/-)) was generated by crossing HLA-A11 transgenic (Tg) mice with HLA-A2(+/+)/DR01(+/+)/H-2-ß2m(-/-)/IAß(-/-) 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 ß2m 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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ratones Transgénicos
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Antígeno HLA-DR1
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Vacunas contra el SIDA
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Vacunas contra Hepatitis B
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Evaluación Preclínica de Medicamentos
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Antígeno HLA-A11
Idioma:
En
Revista:
Hum Vaccin Immunother
Año:
2016
Tipo del documento:
Article
País de afiliación:
China