NR ATNR
AU Bach,P.; Flechsig,E.; Hoffmann,T.; Buchholz,C.J.; Klein,M.A.; Kalinke,U.
TI PrP-displaying retroparticles as a novel tool for mapping the fine specificity of antibodies binding to the cellular form of the prion protein
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-15
PT Konferenz-Poster
AB To activate PrP-specific B cell responses that potentially influence prion pathogenesis, PrP-displaying retroparticles have been generated. We found that such retroparticles expressing murine PrP 121-231 fused to the PDGF receptor (PrPD111) were highly immunogenic in Prnpo/o mice. Interestingly, immunization of wild-type mice with PrPD111-retroparticles resulted in IgM and IgG antibodies specifically binding to the cellular prion protein (PrPc), albeit at considerably lower levels. Thus, PrPD111-retroparticles seemed to be more immunogenic as compared to bacterially expressed PrP or peptide antigens used in other immunization studies. Whereas binding of the PrP-specific monoclonal antibody 6H4 was quantitatively competed by the use of bacterially expressed recombinant PrP, PrPc-specific serum antibodies induced in Prnpo/o mice upon immunization with PrPD111-retroparticles were inhibited only partially. This suggests that PrPc expressed on the surface of PrPD111-retroparticles shared many more antigenic determinants of native PrPc than bacterially expressed PrP. Interestingly, binding of 6H4 and of PrPc-specific serum antibodies were quantitatively inhibited by using PrPD111-retroparticles as competitors. Thus, PrP-retroparticles can be used to define the specificity of antibody binding to native PrPc. Currently, PrP-retroparticles displaying various PrP-deletion mutants are being generated to map the fine specificity of PrP-specific antibodies.
AD Patricia Bach, Ulrich Kalinke, Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany; Eckhard Flechsig, Tanja Hoffmann, Michael Klein, Institute of Virology and Immunobiology, Würzburg, Germany; Christian Buchholz, Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany
SP englisch
PO Deutschland