Methods and products for controlling the immune responses in mammals

Abstract

A method is provided for expressing a mammalian antigen in transformed plants to provide a source of plant material for oral or enteral administration to a mammal to produce tolerance to the antigen.

We claim:  
     
         1 . A method for suppressing or reducing the immune response of a mammal to an antigen comprising orally or enterally administering to the mammal an effective immunosuppressive dose of a plant material derived from a plant transformant capable of producing said antigen or an immunosuppressive fragment or derivative thereof.  
     
     
         2 . A method in accordance with  claim 1  wherein the antigen is a human Major Histocompatibility Complex class II protein.  
     
     
         3 . A method in accordance with  claim 1  wherein the antigen is a human Major Histocompatibility Complex class II α chain.  
     
     
         4 . A method in accordance with  claim 1  wherein the antigen is a human Major Histocompatibility Complex class II β chain.  
     
     
         5 . A method in accordance with  claim 1  wherein the antigen is an autoantigen.  
     
     
         6 . A method in accordance with  claim 1  wherein the antigen is human glutamic acid decarboxylase.  
     
     
         7 . A method on accordance with  claim 5  wherein the autoantigen is involved in the pathogenesis of a disease selected from the group consisting of Type I diabetes mellitus, lupus erythematosis, thyroiditis, multiple sclerosis, uveitis and Crohn's disease.  
     
     
         8 . A method in accordance with any of the preceding claims wherein the plant is transformed with a vector in accordance with  claim 17 .  
     
     
         9 . A method in accordance with any of the preceding claims wherein the plant is selected from the group consisting of potato, tomato, alfalfa and canola.  
     
     
         10 . A method for suppressing the rejection of engrafted donor tissue by a recipient mammal comprising orally or enterally administering to the mammal an effective immunosuppressive dose of a plant material derived from a plant transformant capable of producing a transplantation antigen or an immunosuppressive fragment or derivative of said antigen.  
     
     
         11 . A method in accordance with  claim 10  wherein the antigen is a human Major Histocompatibility Complex protein or an α or β chain thereof.  
     
     
         12 . A method in accordance with any of  claims 10  to  11  wherein the plant is transformed with a vector in accordance with  claim 17 .  
     
     
         13 . A method in accordance with any of the preceding claims wherein the plant material is selected from the group consisting of plant parts, an extract of total plant protein, a partially purified plant protein preparation and a purified plant protein preparation.  
     
     
         14 . A pharmaceutical composition for suppressing or reducing the immune response of a mammal to an antigen comprising an oral or enteral dosage form comprising an effective dose of a plant material derived from a plant transformant capable of producing said antigen or an immunosuppressive fragment or derivative thereof and a pharmaceutically acceptable carrier.  
     
     
         15 . A pharmaceutical composition for suppressing the rejection of engrafted donor tissue by a recipient mammal comprising an oral or enteral dosage form comprising an effective dose of a plant material derived from a plant transformant capable of producing a transplantation antigen or an immunosuppressive fragment or derivative of said antigen and a pharmaceutically acceptable carrier.  
     
     
         16 . A pharmaceutical composition in accordance with  claim 15  wherein the antigen is a human Major Histocompatibility Complex Class II α chain or β chain polypeptide or immunosuppressive fragment or derivative thereof.  
     
     
         17 . A recombinant vector for transformation of a plant host comprising a plant promoter sequence operably linked to a DNA sequence encoding a heterologous polypeptide and a suitable termination sequence in proper reading frame with said DNA sequence.  
     
     
         18 . A recombinant vector in accordance with  claim 17  wherein the heterologous polypeptide is a mammalian protein.  
     
     
         19 . A recombinant vector in accordance with  claim 18  wherein the promoter sequence is the Cauliflower Mosaic Virus 35S promoter, the DNA sequence encodes a human Major Histocompatibility Complex Class II α chain polypeptide or β chain polypeptide and the termination sequence is a nopaline synthase sequence.  
     
     
         20 . A process for producing a human Major Histocompatibility Complex Class II α chain or β chain polypeptide in a plant comprising transforming a plant with the recombinant vector of  claim 19  and expressing the heterologous polypeptide encoded therein.  
     
     
         21 . A recombinant vector in accordance with  claim 18  wherein the promoter sequence is the Cauliflower Mosaic Virus 35S promoter, the DNA sequence encodes human glutamic acid decarboxylase and the termination sequence is a nopaline synthase sequence.  
     
     
         22 . A process for producing human glutamic acid decarboxylase in a plant comprising transforming a plant with the recombinant vector of  claim 21  and expressing the heterologous polypeptide encoded therein.  
     
     
         23 . A recombinant vector in accordance with  claim 18  wherein the mammalian signal-peptide encoding portion of said DNA sequence is replaced by a DNA sequence encoding a plant signal sequence.  
     
     
         24 . A transgenic plant transfected with the recombinant vector of any of  claims 17  to  19 ,  21  or  23 .  
     
     
         25 . A method in accordance with  claim 1  wherein the antigen is a mouse Major Histocompatibility Complex class II protein or an α or β chain thereof.