title: Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein.
abstract: Prion diseases are disorders of protein conformation and do not provoke an immune response. Raising antibodies to the prion protein (PrP) has been difficult due to conservation of the PrP sequence and to inhibitory activity of alpha-PrP antibodies toward lymphocytes. To circumvent these problems, we immunized mice in which the PrP gene was ablated (Prnp 0/0) and retrieved specific monoclonal antibodies (mAbs) through phage display libraries. This approach yielded alpha-PrP mAbs that recognize mouse PrP. Studies with these mAbs suggest that cellular PrP adopts an unusually open structure consistent with the conformational plasticity of this protein.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Williamson
authors.forename: D
authors.initials: D
authors.lastname: Peretz
authors.forename: N
authors.initials: N
authors.lastname: Smorodinsky
authors.forename: R
authors.initials: R
authors.lastname: Bastidas
authors.forename: H
authors.initials: H
authors.lastname: Serban
authors.forename: I
authors.initials: I
authors.lastname: Mehlhorn
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: D R
authors.initials: DR
authors.lastname: Burton
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000918:Antibody Specificity; D001483:Base Sequence; D006224:Cricetinae; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D007108:Immune Tolerance; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D008647:Mesocricetus; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017096:Prion Diseases / Q000276:immunology*; D011328:Prions / Q000032:analysis / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D017931:DNA Primers; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D011328:Prions; D011994:Recombinant Proteins