Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein

R. Anthony Williamson; David Peretz; Nechama Smorodinsky; Raiza Bastidas; Hana Serban; Ingrid Mehlhorn; Stephen J. Dearmond; Stanley B. Prusiner; Dennis R. Burton

doi:10.1073/pnas.93.14.7279

Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein

R. Anthony Williamson, David Peretz, Nechama Smorodinsky, Raiza Bastidas, Hana Serban, Ingrid Mehlhorn, Stephen J. Dearmond, Stanley B. Prusiner, Dennis R. Burton^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

102 Scopus citations

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 α-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 α-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.

Original language	English
Pages (from-to)	7279-7282
Number of pages	4
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	93
Issue number	14
DOIs	https://doi.org/10.1073/pnas.93.14.7279
State	Published - 9 Jul 1996
Externally published	Yes

Funding

Funders	Funder number
National Institute on Aging	P01AG002132

Keywords

gene ablation
mouse antibody libraries
phage display
prion disease
scrapie

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10.1073/pnas.93.14.7279

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Williamson, R. A., Peretz, D., Smorodinsky, N., Bastidas, R., Serban, H., Mehlhorn, I., Dearmond, S. J., Prusiner, S. B., & Burton, D. R. (1996). Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein. Proceedings of the National Academy of Sciences of the United States of America, 93(14), 7279-7282. https://doi.org/10.1073/pnas.93.14.7279

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Williamson, RA, Peretz, D, Smorodinsky, N, Bastidas, R, Serban, H, Mehlhorn, I, Dearmond, SJ, Prusiner, SB & Burton, DR 1996, 'Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein', Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 14, pp. 7279-7282. https://doi.org/10.1073/pnas.93.14.7279

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AU - Peretz, David

AU - Smorodinsky, Nechama

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AU - Mehlhorn, Ingrid

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AU - Burton, Dennis R.

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AB - 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 α-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 α-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.

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Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein

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Keywords

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