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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 fromhamster, sheep, cattle and deer. A linear epitope of mAb T1 was identified at residues 137-143 of MoPrP and buried in PrPC expressed on the cell surface. mAb T1 showed no inhibitory effect on accumulation of PrPSc 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 PrPC.mAb T2 showed an excellent inhibitory effect onPrPSc accumulation in vitro at a50%inhibitory concentration of 0.02 μg/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 PrPSc accumulation, suggesting that scFv T2 could potentially be an immunotherapeutic tool for prion diseases by inhibition of PrPSc accumulation.

Original languageEnglish
Pages (from-to)112-121
Number of pages10
JournalMICROBIOLOGY and IMMUNOLOGY
Volume54
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

Keywords

  • Anti-prion effect
  • Monoclonal antibody
  • Single-chain fragment variable region

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology

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