An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection.
Journal
  Journal of immunology (Baltimore, Md. : 1950)
Citation
  J Immunol. 177(11):8037-45
Publication date
  2006 Dec 1
Authors
  Hu J
Peng X
Schell TD
Budgeon LR
Cladel NM
Christensen ND
Investigators
  Neil D. Christensen
Jianming Hu
Xuwen Peng
Todd Schell
Grant agencies
  National Cancer Institute
Grants
  NCI R01 CA 47622
MeSH headings
  Animals, Genetically Modified
CD8-Positive T-Lymphocytes
HLA-A2 Antigen
Host-Parasite Interactions
Papillomavirus Infections
Rabbits
MeSH qualifiers
  immunology
genetics
Abstract
  We have established several HLA-A2.1-transgenic rabbit lines to provide a host to study CD8(+) T cell responses during virus infections. HLA-A2.1 protein expression was detected on cell surfaces within various organ tissues. Continuous cultured cells from these transgenic rabbits were capable of presenting both endogenous and exogenous HLA-A2.1-restricted epitopes to an HLA-A2.1-restricted epitope-specific CTL clone. A DNA vaccine containing an HLA-A2.1-restricted human papillomavirus type 16 E7 epitope (amino acid residues 82-90) stimulated epitope-specific CTLs in both PBLs and spleen cells of transgenic rabbits. In addition, vaccinated transgenic rabbits were protected against infection with a mutant cottontail rabbit papillomavirus DNA containing an embedded human papillomavirus type 16 E7/82-90 epitope. Complete protection was achieved using a multivalent epitope DNA vaccine based on epitope selection from cottontail rabbit papillomavirus E1 using MHC class I epitope prediction software. HLA-A2.1-transgenic rabbits will be an important preclinical animal model system to study virus-host interactions and to assess specific targets for immunotherapy.