Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein

被引：100

作者：

Williamson, RA

Peretz, D

Smorodinsky, N

Bastidas, R

Serban, H

Mehlhorn, I

DeArmond, SJ

Prusiner, SB

Burton, DR

机构：

[1] Scripps Res Inst, RES INST, DEPT IMMUNOL, LA JOLLA, CA 92037 USA

[2] Scripps Res Inst, RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA

[3] UNIV CALIF SAN FRANCISCO, DEPT NEUROL, SAN FRANCISCO, CA 94143 USA

[4] UNIV CALIF SAN FRANCISCO, DEPT BIOCHEM & BIOPHYS, SAN FRANCISCO, CA 94143 USA

[5] UNIV CALIF SAN FRANCISCO, DEPT PATHOL, SAN FRANCISCO, CA 94143 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1996年 / 93卷 / 14期

关键词：

mouse antibody libraries; phage display; gene ablation; scrapie; prion disease;

D O I：

10.1073/pnas.93.14.7279

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：7279 / 7282

页数：4

共 41 条

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