Diagnostic and therapeutic epitope, and transgenic plant

Abstract

A method of diagnosing coeliac disease, or susceptibility to coeliac disease, in an individual comprising: (a) contacting a sample from the host with an agent selected from (i) the epitope comprising sequence which is: SEQ ID NO:1 or 2, or an equivalent sequence from a naturally occurring homologue of the gliadin represented by SEQ ID NO:3, (ii) an epitope comprising sequence comprising: SEQ ID NO:1, or an equivalent sequence from a naturally occurring homologue of the gliadin represented by SEQ ID NO:3, which epitope is an isolated oligopeptide derived from a gliadin protein, (iii) an analogue of (i) or (ii) which is capable of being recognised by a T cell receptor that recognises (i) or (ii), which in the case of a peptide analogue is not more than 50 amino acids in length, or (iv) a product comprising two or more agents as defined in (i), (ii) or (iii), and (b) determining in vitro whether T cells in the sample recognise the agent; recognition by the T cells indicating that the individual has, or is susceptible to, coeliac disease. Therapeutic compositions which comprise the epitope and gliadin proteins which do not cause coeliac disease are also provided.

1 - 59 . (canceled) 
     
     
         60 . A method of inducing tolerization of a subject to exposure to A-gliadin, comprising:
 administering to the subject a peptide comprising the sequence QPFPQPELPYPQP in an amount and for a period of time effective to induce a decrease in the production of a T-cell- and/or antibody response in the subject to the exposure to transglutamidated A-gliadin, or a fragment of transglutamidated A-gliadin, comprising said sequence, thereby tolerizing the subject to said A-gliadin protein;   wherein the peptide is 15-17 amino acids in length; and   wherein the subject has or is susceptible to have coeliac disease.   
     
     
         61 . The method of  claim 60 , wherein the peptide comprises the sequence LQPFPQPELPYPQPQ. 
     
     
         62 . The method of  claim 60  or  61 , wherein the peptide is 16 amino acids in length. 
     
     
         63 . The method of  claim 60  or  61 , wherein the peptide is administered to the subject intradermally or subcutaneously. 
     
     
         64 . The method of  claim 60 , wherein the subject has been diagnosed with coeliac disease, or susceptibility to having coeliac disease, prior to the administering by a method comprising:
 a) contacting a sample comprising T-cells from the subject with a peptide comprising the sequence PQPELPY (SEQ ID NO: 1); and   b) determining in vitro whether T-cells in the sample recognize the peptide, wherein recognition by the T-cells indicates that the subject has, or is susceptible to having, coeliac disease.   
     
     
         65 . The method of  claim 64 , wherein the sample is a peripheral blood sample. 
     
     
         66 . The method of  claim 64 , wherein the recognition of the peptide by the T-cells is determined by detecting the secretion of a cytokine from the T-cells. 
     
     
         67 . The method of  claim 66 , wherein the cytokine is IFN-γ. 
     
     
         68 . The method of  claim 66 , wherein the cytokine is detected by allowing the cytokine to bind to an immobilized antibody specific to the cytokine and then detecting the presence of the antibody/cytokine complex. 
     
     
         69 . The method of  claim 67 , wherein the IFN-γ is detected by allowing the IFN-γ to bind to an immobilized antibody specific to IFN-γ and then detecting the presence of the antibody/IFN-γ complex. 
     
     
         70 . The method of  claim 64 , wherein the determining is carried out by measuring whether the peptide binds the T-cell receptor. 
     
     
         71 . The method of  claim 60 , wherein the subject has been diagnosed with coeliac disease, or susceptibility to having coeliac disease, prior to the administering, by a method comprising determining whether T-cells of the subject recognize the peptide, wherein recognition by the T-cells indicates that the subject has, or is susceptible to having, coeliac disease. 
     
     
         72 . The method of  claim 71 , wherein the diagnosing comprises administering the peptide to the skin of the subject and detecting the presence of inflammation at the site of administration, wherein the detection of inflammation indicates that T-cells of the subject recognize the peptide. 
     
     
         73 . The method of  claim 60 , wherein the subject has been diagnosed with coeliac disease, or susceptibility to having coeliac disease, prior to the administering, by a method comprising determining the presence of an antibody that binds to the peptide in a sample from the subject, wherein the presence of the antibody indicates that the subject has, or is susceptible to having, coeliac disease, and wherein the sample is a peripheral blood sample. 
     
     
         74 . A method of targeting T-cells in a subject, comprising
 administering to the subject a peptide comprising the sequence QPFPQPELPYPQP, wherein the peptide is 15-17 amino acids in length and   wherein the subject has or is susceptible to have coeliac disease.   
     
     
         75 . The method of  claim 74 , wherein the peptide comprises the sequence LQPFPQPELPYPQPQ. 
     
     
         76 . The method of  claim 74  or  75 , wherein the peptide is 16 amino acids in length. 
     
     
         77 . The method of any one of  claim 74  or  75 , wherein the peptide is administered to the subject intradermally or subcutaneously. 
     
     
         78 . The method of  claim 76 , wherein the peptide is administered to the subject intradermally or subcutaneously.