CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils
| Autor: | Jae I. I. Kim, William R. Levis, Xuemin Ye, Daryl S. Spinner, Georgia Schuller-Levis, Richard J. Kascsak, Thomas Wisniewski, Michael Flory, Giuseppe LaFauci, Richard I. Carp, Harry C. Meeker, Regina Kascsak |
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| Rok vydání: | 2007 |
| Předmět: |
PrPSc Proteins
CpG Oligodeoxynucleotide medicine.drug_class animal diseases Immunology Monoclonal antibody Epitope PRNP Epitopes Mice Th2 Cells Immune system medicine Animals Immunology and Allergy Mice Knockout Innate immune system biology Antibodies Monoclonal TLR9 DNA Cell Biology Th1 Cells Immunoglobulin Class Switching Virology Molecular biology Immunity Innate PrP 27-30 Protein nervous system diseases Oligodeoxyribonucleotides Toll-Like Receptor 9 Antibody Formation biology.protein Immunization Antibody |
| Zdroj: | Journal of Leukocyte Biology. 81:1374-1385 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.1106665 |
| Popis: | Prion diseases are characterized by conversion of the cellular prion protein (PrP C )t o a protease-resistant conformer, the srapie form of PrP (PrP Sc ). Humoral immune responses to non- denatured forms of PrP Sc have never been fully characterized. We investigated whether produc- tion of antibodies to PrP Sc could occur in PrP null (Prnp / ) mice and further, whether innate im- mune stimulation with the TLR9 agonist CpG oli- godeoxynucleotide (ODN) 1826 could enhance this process. Whether such stimulation could raise anti-PrP Sc antibody levels in wild-type (Prnp / ) mice was also investigated. Prnp / and Prnp / mice were immunized with nondenatured 139A scrapie-associated fibrils (SAF), with or without ODN 1826, and were tested for titers of PrP- specific antibodies. In Prnp / mice, inclusion of ODN 1826 in the immunization regime increased anti-PrP titers more than 13-fold after two immu- nizations and induced, among others, antibodies to an N-terminal epitope, which were only present in the immune repertoire of mice receiving ODN 1826. mAb 6D11, derived from such a mouse, reacts with the N-terminal epitope QWNK in native and denatured forms of PrP Sc and recombinant PrP and exhibits a Kd in the 10 11 M range. In Prnp / mice, ODN 1826 increased anti-PrP lev- els as much as 84% after a single immunization. Thus, ODN 1826 potentiates adaptive immune re- sponses to PrP Sc in 139A SAF-immunized mice. These results represent the first characterization of humoral immune responses to nondenatured, in- fectious PrP Sc and suggest methods for optimizing the generation of mAbs to PrP Sc , many of which could be used for diagnosis and treatment of prion diseases. J. Leukoc. Biol. 81: 1374-1385; 2007. |
| Databáze: | OpenAIRE |
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