An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection.
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.
Hu
Jiafen
J
Jake Gittlen Cancer Research Foundation, and Department of Pathology, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
Peng
Xuwen
X
Schell
Todd D
TD
Budgeon
Lynn R
LR
Cladel
Nancy M
NM
Christensen
Neil D
ND
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D012777:Cottontail rabbit papillomavirus / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D030361:Papillomavirus Infections / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000276:immunology; D011817:Rabbits / Q000235:genetics*; D012984:Software; D019076:Transgenes; D019444:Vaccines, DNA / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA