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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-2Db 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.
Abbreviations
| MHC | = | major histocompatibility complex |
| HLA | = | human leukocyte antigen |
| CTL | = | cytotoxic T lymphocyte |
| HIV | = | human immunodeficiency virus |
| HBV | = | hepatitis B virus |
Funding
This work was supported by the National Program of Infectious Diseases (No. 2012ZX10004–502 and No.2011ZXJ09201–031), the Basic Research 973 Project (2011CB504706).
Disclosure of potential conflicts of interest
All authors agree to submit our manuscript to Human Vaccines & Immunotherapeutics. None of the authors have any conflicts of interest to declare.