A novel antigen-toxin chimeric protein: Myelin-basic protein- pseudomonas exotoxin (MBP-PE 40) for treatment of experimental autoimmune encephalomyelitis

Talma Brenner, Ida Steinberger, Dov Soffer, Evelyne Beraud, Abraham Ben-Nun, Haya Lorberboum-Galski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Myelin basic protein (MBP), is a major component of the central nervous system (CNS) myelin. MBP can stimulate T cells that migrate into the CNS, initiating a cascade of events that result in perivascular infiltration and demyelination. EAE is an inflammatory and demyelinating autoimmune disease of the CNS that serves as a model for the human disease Multiple Sclerosis (MS). Taking advantage of the fact that EAE can be mediated by T cells, able to recognize MBP or its peptides, we developed a new approach to target anti- MBP T cells by fusing an MBP-sequence to a toxin. In the new chimeric protein, an oligonucleotide coding for the guinea pig MBP encephalitogenic moiety (residues 68-88) was fused to a cDNA encoding a truncated form of the PE gene (PE40). The chimeric gene termed MBP-PE was expressed in E. coli and highly purified. MBP-PE chimeric protein was cytotoxic to various anti-MBP T cells. Moreover, treatment with the novel MBP-toxin blocked the clinical signs of EAE as well as CNS inflammation and demyelination. A chimeric protein such as MBP-PE40 presents a novel prototype of chimeric proteins, composed of antigen/peptide-toxin, that could prove to be an efficient and specific immunotherapeutic agent for autoimmune diseases in which a known antigen is involved.

Original languageAmerican English
Pages (from-to)403-410
Number of pages8
JournalImmunology Letters
Volume68
Issue number2-3
DOIs
StatePublished - 1 Jun 1999
Externally publishedYes

Keywords

  • Chimeric protein
  • EAE
  • Myelin basic protein
  • Pseudomonas exotoxin
  • Targeting

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