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

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.

journal_name

Immunol Lett

journal_title

Immunology letters

authors

Brenner T,Steinberger I,Soffer D,Beraud E,Ben-Nun A,Lorberboum-Galski H

doi

10.1016/s0165-2478(99)00089-9

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

403-10

issue

2-3

eissn

0165-2478

issn

1879-0542

pii

S0165-2478(99)00089-9

journal_volume

68

pub_type

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