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.
|
Authors | T Brenner, I Steinberger, D Soffer, E Beraud, A Ben-Nun, H Lorberboum-Galski |
Journal | Immunology letters
(Immunol Lett)
Vol. 68
Issue 2-3
Pg. 403-10
(Jun 01 1999)
ISSN: 0165-2478 [Print] Netherlands |
PMID | 10424450
(Publication Type: Journal Article)
|
Chemical References |
- Exotoxins
- Immunotoxins
- MBP-PE40
- Myelin Basic Protein
- Recombinant Fusion Proteins
- ADP Ribose Transferases
|
Topics |
- ADP Ribose Transferases
- Acute Disease
- Animals
- Cell Line
- Encephalomyelitis, Autoimmune, Experimental
(drug therapy, pathology)
- Exotoxins
(therapeutic use, toxicity)
- Female
- Immunotoxins
(therapeutic use)
- Mice
- Myelin Basic Protein
(therapeutic use, toxicity)
- Recombinant Fusion Proteins
(therapeutic use)
- T-Lymphocytes
(cytology, drug effects)
|