T cell epitopes of the cyn d 1 allergen from bermuda grass pollen

Abstract

The present invention relates generally to molecules such as peptides, polypeptides and proteins which interact immunologically with T cell lymphocytes in subjects having Bermuda grass allergy and genetic sequences encoding same. These molecules are preferentially immunointeractive with T cells in subjects having a Bermuda grass pollen allergy. The molecules of the present invention are useful in the development of diagnostic, therapeutic and prophylactic agents for conditions characterised by an aberrant, inappropriate or otherwise unwanted immune response to Bermuda grass pollen or derivative or homologue thereof.

1 . An isolated peptide of the formula:  
         X 1 X 2 X 3    
       wherein: 
 X 1  and X 3  may be the same or different and each is an amino acid sequence comprising from 0 to 40 naturally or non-naturally occurring amino acid residues;  
 X 2  is any amino acid sequence derived from or homologues to Cyn d 1,  
 and wherein said peptide molecule is capable of interacting with T cells and modifying T cell function when incubated with cells from subjects having a condition characterized by an aberrant, unwanted or otherwise inappropriate immune response to Cyn d 1 or a derivative, homologue, mutant, chemical equivalent or mimetic of said peptide.  
 
     
     
         2 . The peptide according to  claim 1  wherein X 2  is an amino acid sequence of from 5 to 100 residues derived from, homologous to or contiguous with amino acids 1-246 inclusive or derivatives thereof of Cyn d 1.  
     
     
         3 . The peptide according to  claim 2  wherein said amino acid sequence is derived from, homologous to or contiguous with amino acids 91-128, 163-209 or 217-246 inclusive or derivatives thereof of Cyn d 1.  
     
     
         4 . The peptide according to  claim 2  wherein said amino acid sequence is derived from, homologous to or contiguous with amino acids 91-110, 100-119, 109-128, 163-182, 172-191, 181-200, 191-209, 217-236and/or222-241 inclusive or derivatives thereof of Cyn d 1.  
     
     
         5 . The peptide according to  claim 4  wherein said amino aid sequence is derived from, homologous to or contiguous with amino acids 109-128, 181-209 and/or 217-241 inclusive or derivatives thereof of Cyn d 1.  
     
     
         6 . The peptide according to  claim 5  wherein said amino acids are 109-128 inclusive or derivatives thereof of Cyn d 1.  
     
     
         7 . The peptide according to  claim 5  wherein said amino acids are 181-200 and/or 190-209 inclusive or derivatives thereof of Cyn d 1.  
     
     
         8 . A peptide according to  claim 5  wherein said amino acids are 217-236 and/or 222-241 inclusive or derivatives thereof of Cyn d 1.  
     
     
         9 . The peptide according to  claim 2  wherein said amino acid sequence comprises at least 5 amino acids derived form one or more of the following amino acid sequences:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   SGKAFGAMAKKGQEDKLRKA 
                   (SEQ ID NO: 14) 
                     
                 
                     
                     
                 
                     
                   PKDSDEFIPMKSSWGAIWRI 
                   (SEQ ID NO: 22) 
                 
                     
                     
                 
                     
                   MKSSWGAIWRIDPKKPLKGP 
                   (SEQ ID NO: 23) 
                 
                     
                     
                 
                     
                   EGGAHLVQDDVIPANWKPDT 
                   (SEQ D NO: 26) 
                 
                     
                     
                 
                     
                   LVQDDVIPANWKPDTVYTSK. 
                   (SEQ ID NO: 27) 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         10 . The peptide according to  claim 8  wherein said amino acid sequence is derived from one or more of SEQ ID NO: 14 or SEQ ID NO: 26.  
     
     
         11 . An isolated peptide comprising an amino acid sequence derived from or homologous to Cyn d 1 wherein said peptide molecule is capable of interacting with T cells and modifying T cell function when incubated with cells from subjects having a condition characterized by an aberrant, unwanted or otherwise inappropriate immune response to Cyn d 1 or a derivative, homologue, analogue, mutant, chemical equivalent or mimetic of said peptide.  
     
     
         12 . The peptide according to  claim 11  wherein said amino acid sequence is of 5-100 residues derived from, homologous to or contiguous with amino acids 1-246 inclusive or derivatives thereof of Cyn d 1.  
     
     
         13 . The peptide according to  claim 12  wherein said amino acid sequence is derived from, homologous to or contiguous with amino acids 91-128, 163-209 or 217-246 inclusive or derivatives thereof of Cyn d 1.  
     
     
         14 . The peptide according to  claim 12  wherein said amino acid sequence is derived from, homologous to or contiguous with amino acids 91-110, 100-119, 109-128, 163-182, 172-191, 181-200, 190-209, 217-236 and/or 222-241 inclusive or derivatives thereof of Cyn d 1.  
     
     
         15 . The peptide according to  claim 14  wherein said amino acid sequence is derived from, homologous to or contiguous with amino acids 109-128, 181-209 and/or 217-241 inclusive or derivatives thereof of Cyn d 1.  
     
     
         16 . The peptide according to  claim 15  wherein said amino acids are 109-128 inclusive or derivatives thereof of Cyn d 1.  
     
     
         17 . The peptide according to  claim 15  wherein said amino acids are 181-200 and/or 190-209 inclusive or derivatives thereof of Cyn d 1.  
     
     
         18 . The peptide according to  claim 15  wherein said amino acids are 217-236 and/or 222-241 inclusive or derivatives thereof of Cyn d 1.  
     
     
         19 . The peptide according to  claim 15  wherein said amino acid sequence comprises at least 5 amino acids derived from one or more of the following amino acid sequences:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   SGKAFGAMAKKGQEDKLRKA 
                   (SEQ ID NO: 14) 
                     
                 
                     
                     
                 
                     
                   PKDSDEFIPMKSSWGAIWRI 
                   (SEQ ID NO: 22) 
                 
                     
                     
                 
                     
                   MKSSWGAIWRIDPKKPLKGP 
                   (SEQ ID NO: 23) 
                 
                     
                     
                 
                     
                   EGGAHLVQDDVIPANWKPDT 
                   (SEQ ID NO: 26) 
                 
                     
                     
                 
                     
                   LVQDDVIPANWKPDTVYTSK. 
                   (SEQ ID NO: 27) 
                 
                     
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         20 . The peptide according to  claim 19  wherein said amino acid sequence is derived from one or more of SEQ ID NO: 14 or SEQ ID NO: 26.  
     
     
         21 . An isolated nucleic acid molecule comprising a sequence of nucleotide encoding or complementary to a sequence encoding a peptide according to  claim 1  or  11 .  
     
     
         22 . A method for the treatment and/or prophylaxis of a condition in a subject, which condition is characterized by an aberrant, unwanted or otherwise inappropriate immune response to Cyn d 1, said method comprising administering to said subject an effective amount of a peptide according to  claim 1  or  11  for a time and under conditions sufficient to remove or reduce the presence or function in said subject of T cells and/or antibodies directed to said Cyn d 1.  
     
     
         23 . The method according to  claim 22  wherein said condition is Bermuda grass pollen hypersensitivity.  
     
     
         24 . Use of a peptide according to  claim 1  or  11  in the manufacture of a medicament for the treatment of a condition in a mammal which condition is characterized by an aberrant, unwanted or otherwise inappropriate immune response to Cyn d 1.  
     
     
         25 . Use according to  claim 24  wherein said condition is Bermuda grass pollen hypersensitivity.  
     
     
         26 . A pharmaceutical composition comprising a peptide to  claim 1  or  11  together with one or more pharmaceutically acceptable carriers and/or diluents.  
     
     
         27 . A method of diagnosing or monitoring a condition in a mammal, which condition is characterized by an aberrant, unwanted or inappropriate response to Cyn d 1, said method comprising screening for Cyn d 1 reactive T cells and/or antibodies utilizing the peptides according to  claim 1  or  11 .  
     
     
         28 . The method according to  claim 27  wherein said condition is Bermuda grass pollen hypersensitivity.  
     
     
         29 . A diagnostic kit for use in the method of diagnosing or monitoring a condition in a mammal, which condition is characterized by an aberrant, unwanted or inappropriate response to Cyn d 1, wherein said kit comprises a peptide according to  claim 1  or  11 .