Construction and use of genes encoding pathogenic epitopes for treatment of autoimmune disease

Abstract

The present invention relates to the application of genetic engineering to provide a treatment of autoimmune disease. This is achieved preferably through the introduction of one or more recombinant genes encoding self antigens which are the target of an autoimmune response. In particular the invention provides a method of designing and constructing a gene encoding an encephalitogenic epitope of proteolipid protein, and to the in vivo expression of the gene product by a recombinant retroviral vector. The expression and secretion of the encephalitogenic epitope ameliorates the histopathological and clinical characteristics of experimental autoimmune encephalomyelitis (EAE) in the mouse model for multiple sclerosis (MS).

What is claimed is:  
     
         1 . A method of treating a patient for a T-cell mediated autoimmune disease comprising: 
 introducing a cell comprising a polynucleotide encoding an antigenic amino acid sequence into a patient, the cell expressing in the patient a therapeutically effective amount of the antigenic amino acid sequence to induce T-cell tolerance to the expressed antigenic amino acid sequence.    
     
     
         2 . The method of  claim 1  wherein the patient is human.  
     
     
         3 . The method of  claim 2  wherein the cell is a fibroblast.  
     
     
         4 . The method of  claim 3  wherein the fibroblast is histocompatible with the patient.  
     
     
         5 . The method of  claim 1  wherein the cell is autologous.  
     
     
         6 . The method of  claim 1  wherein the cell is heterologous.  
     
     
         7 . The method of  claim 1  wherein the antigenic amino acid sequence is from a nervous system protein.  
     
     
         8 . The method of  claim 2  wherein the disease is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, juvenile onset diabetes, Sjogren's disease, thyroid disease, myasthenia gravis, and chronic inflammatory demyelinating polyneuropathy (CIDP).  
     
     
         9 . The method of  claim 8  wherein the disease is multiple sclerosis.  
     
     
         10 . The method of  claim 1 , wherein the expressed antigenic amino acid further comprises a hydrophobic leader sequence, the hydrophobic leader sequence enabling the antigenic amino acid to be synthesized in an endoplasmic reticulum for later constitutive secretion.  
     
     
         11 . The method of  claim 1 , wherein the polynucleotide further comprises a Kozak box, the Kozak box permitting efficient translation of an mRNA transcribed from the polynucleotide.  
     
     
         12 . The method of  claim 1 , wherein the antigenic amino acid sequence comprises an encephalogenic amino acid epitope.  
     
     
         13 . The method of  claim 12 , wherein the encephalogenic amino acid epitope is selected from the group consisting of the encephalogenic epitopes of myelin basic protein, myelin-oligodendrocyte glycoprotein, and proteolipid protein.  
     
     
         14 . The method of  claim 13  wherein the disease is multiple sclerosis.  
     
     
         15 . The method of  claim 1 , wherein a recombinant vector is used to transfect the polynucleotide into the cell.  
     
     
         16 . The method of  claim 15 , wherein the vector is a viral vector.  
     
     
         17 . The method of  claim 16 , wherein the viral vector is a retroviral vector.  
     
     
         18 . The method of  claim 15 , wherein the transfection is in vitro.  
     
     
         19 . The method of  claim 15 , wherein the transfection is in vivo.