规避耐受性以产生针对朊病毒蛋白的自体单克隆抗体。

Williamson R A, Peretz D, Smorodinsky N, Bastidas R, Serban H, Mehlhorn I, DeArmond S J, Prusiner S B, Burton D R

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7279-82. doi: 10.1073/pnas.93.14.7279.

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.

朊病毒疾病是蛋白质构象紊乱疾病，不会引发免疫反应。由于朊病毒蛋白（PrP）序列的保守性以及α-PrP抗体对淋巴细胞的抑制活性，制备针对PrP的抗体一直很困难。为了克服这些问题，我们用PrP基因缺失的小鼠（Prnp 0/0）进行免疫，并通过噬菌体展示文库获得了特异性单克隆抗体（mAb）。这种方法产生了识别小鼠PrP的α-PrP mAb。对这些mAb的研究表明，细胞PrP具有异常开放的结构，这与该蛋白质的构象可塑性一致。