Aquaporin-4 Peptide Compositions and Methods of Use

Abstract

The present disclosure provides human Aquaporin 4 (AQP4) peptides and peptides having homology to human Aquaporin 4 (AQP4) peptides. Also provided herein are methods for using human AQP4 peptides and peptides homologous to human AQP4 peptides for diagnosing and/or treating Neuromyelitis Optica.

1 . A composition comprising:
 a peptide comprising a contiguous stretch of amino acids having the consensus amino acid sequence:   
       
         
           
                 
                 
               
                     
                   Leu-Pro-X 1 -X 2 -Met-X 3 -X 4 -Ile-X 5 -X 6   
                 
             
                
               
            
           
         
         wherein the peptide is up to 50 amino acids in length, and 
         wherein X 1  is Val (V) or Ile (I), 
         X 2  is Ser (S) or Asp (D), 
         X 3  is Val (V), Ile (I), or Gly (G), 
         X 4  is Leu (L) or Ile (I), 
         X 5  is Met (M) or Ser (S), 
         and X 6  is Leu (L), Val (V), or Ala (A). 
       
     
     
         2 . The composition of  claim 1 , wherein:
 X 1  is Val (V),   X 2  is Ser (S) or Asp (D),   X 3  is Val (V),   X 4  is Leu (L),   X 5  is Ser (S),   and X 6  is Leu (L).   
     
     
         3 . A composition comprising:
 a peptide comprising a contiguous stretch of amino acids having the consensus amino acid sequence:   
       
         
           
                 
                 
               
                     
                   LPVXMVLISL 
                 
             
                
               
            
           
         
         wherein the peptide is up to 50 amino acids in length, and 
         wherein X is Asp or Ser. 
       
     
     
         4 . A composition comprising a peptide comprising a contiguous stretch of amino acids having the sequence: 
       
         
           
                 
                 
               
                     
                   GILYLVTPPSVVGGLGVTMV 
                 
             
                
               
            
           
         
         wherein the peptide is up to 50 amino acids in length. 
       
     
     
         5 . A composition comprising a peptide comprising a contiguous stretch of amino acids having the sequence: 
       
         
           
                 
                 
               
                     
                   SMNPARSFGPAVIMGNWENH 
                 
             
                
               
            
           
         
         wherein the peptide is up to 50 amino acids in length. 
       
     
     
         6 . A composition comprising a peptide comprising a contiguous stretch of amino acids having the sequence: 
       
         
           
                 
                 
               
                     
                   AGHGLLVELIITFQL 
                 
             
                
               
            
           
         
         wherein the peptide is up to 50 amino acids in length. 
       
     
     
         7 . A composition comprising a peptide comprising a contiguous stretch of amino acids having the sequence: 
       
         
           
                 
                 
               
                     
                   RFKEAFSKAAQQTKGSYMEV 
                 
             
                
               
            
           
         
         wherein the peptide is up to 50 amino acids in length. 
       
     
     
         8 . The composition of  claim 1 , wherein the peptide is 5-30 amino acids in length. 
     
     
         9 . The composition of  claim 1 , wherein the peptide is 10-20 amino acids in length. 
     
     
         10 . A method of diagnosing Neuromyelitis Optica (NMO) in a subject, the method comprising:
 contacting a sample from the subject with a peptide of  claim 1 ; and   measuring the number of T cells, wherein an increase in the number of T cells as compared to a control indicates that the subject has NMO.   
     
     
         11 . The method of  claim 10 , wherein the T cells are T helper 17 (Th17) T cells. 
     
     
         12 . The method of  claim 10 , wherein the T cells are CD4 +  T cells. 
     
     
         13 . The method of  claim 10 , wherein the peptide is 5-30 amino acids in length. 
     
     
         14 . The method of  claim 10 , wherein the peptide is 10-20 amino acids in length. 
     
     
         15 . A method for screening for candidate agents for inhibiting proliferation of T cells, the method comprising:
 contacting a T cell obtained from a subject having Neuromyelitis Optica with:
 a peptide  claim 1 , and 
 a candidate agent; 
   measuring the number of T cells, wherein a decrease in the number of T cells as compared to a control indicates that the candidate agent inhibits proliferation of T cells.   
     
     
         16 . The method of  claim 15 , wherein the T cells are T helper 17 (Th17) T cells. 
     
     
         17 . The method of  claim 15 , wherein the T cells are CD4 +  T cells. 
     
     
         18 . The method of  claim 15 , wherein the peptide is 5-30 amino acids in length. 
     
     
         19 . The method of  claim 15 , wherein the peptide is 10-20 amino acids in length. 
     
     
         20 . A method for inducing immune tolerance to AQP-4 protein and fragments thereof in a subject, the method comprising:
 administering an effective dose of the composition of  claim 1  to a subject,
 wherein the administering the peptide induces immune tolerance to AQP-4 protein and fragments thereof in the subject. 
   
     
     
         21 . The method of  claim 20 , wherein the peptide is 5-30 amino acids in length. 
     
     
         22 . The method of  claim 20 , wherein the peptide is 10-20 amino acids in length.