Mamu-A*01/K{sup b} transgenic and MHC Class I knockout mice as a tool for HIV vaccine development
- Division of Translational Vaccine Research, Fox South, 1000B, Beckman Research Institute of the City of Hope, 1500 E. Duarte Rd., Comprehensive Cancer Center, Duarte, CA 91010 (United States)
- Animal Resource Center, City of Hope Comprehensive Cancer Center, Duarte, CA (United States)
- Transgenic Mouse Core Facility, City of Hope Comprehensive Cancer Center, Duarte, CA (United States)
- Department of Pathology and Laboratory Medicine, University of California, Davis, CA (United States)
- Beckman Research Institute of the City of Hope, Division of Information Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA (United States)
We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (alpha1 and alpha2 Mamu-A*01 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2K{sup b} domains) MHC Class I molecules were derived by transgenesis of the H-2K{sup b}D{sup b} double MHC Class I knockout strain. After immunization of Mamu-A*01/K{sup b} Tg mice with rVV-SIVGag-Pol, the mice generated CD8{sup +} T-cell IFN-gamma responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/K{sup b} Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.
- OSTI ID:
- 21357503
- Journal Information:
- Virology, Vol. 387, Issue 1; Other Information: DOI: 10.1016/j.virol.2009.01.041; PII: S0042-6822(09)00074-9; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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