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A Novel Anti-Prion Protein Monoclonal Antibody and Its Single-Chain Fragment Variable Derivative With Ability to Inhibit Abnormal Prion Protein Accumulation in Cultured Cells

Yoshihisa Shimizu, Yuko Kaku-Ushiki, Yoshifumi Iwamaru, Tamaki Muramoto, Tetsuyuki Kitamoto, Takashi Yokoyama, Shirou Mohri, Yuichi Tagawa

Microbiol Immunol. 2010 Feb;54(2):112-21.

PMID: 20377745

Abstract:

mAbs T1 and T2 were established by immunizing PrP gene ablated mice with recombinant MoPrP of residues 121-231. Both mAbs were cross-reactive with PrP from hamster, sheep, cattle and deer. A linear epitope of mAb T1 was identified at residues 137-143 of MoPrP and buried in PrP(C) expressed on the cell surface. mAb T1 showed no inhibitory effect on accumulation of PrP(Sc) in cultured scrapie-infected neuroblastoma (ScN2a) cells. In contrast, mAb T2 recognized a discontinuous epitope ranged on, or structured by, residues 132-217 and this epitope was exposed on the cell surface PrP(C). mAb T2 showed an excellent inhibitory effect on PrP(Sc) accumulation in vitro at a 50% inhibitory concentration of 0.02 microg/ml (0.14 nM). The scFv form of mAb T2 (scFv T2) was secreted in neuroblastoma (N2a58) cell cultures by transfection through eukaryotic secretion vector. Coculturing of ScN2a cells with scFv T2-producing N2a58 cells induced a clear inhibitory effect on PrP(Sc) accumulation, suggesting that scFv T2 could potentially be an immunotherapeutic tool for prion diseases by inhibition of PrP(Sc) accumulation.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4247953 Monoclonal Anti-Prion Protein antibody produced in mouse Monoclonal Anti-Prion Protein antibody produced in mouse Price
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