METHODS OF DE-EPITOPING WHEAT PROTEINS AND USE OF SAME FOR THE TREATMENT OF CELIAC DISEASE

1 . A method for identifying an epitope of a wheat T cell immunogen, the method comprising identifying an epitope on the wheat T cell immunogen for the ability to bind a major histocompatibility complex (MHC) class II, thereby identifying the epitope of a wheat T cell immunogen.

2 . A method for de-epitoping a wheat polypeptide, the method comprising mutating one or more amino acid residues of a celiac-associated epitope on the wheat polypeptide to generate a de-epitoped polypeptide having one or more mutation in said celiac-associated epitope, thereby de-epitoping the wheat polypeptide.

3 . The method of claim 1 , wherein said epitope is a celiac-associated epitope.

4 . The method of claim 2 , wherein said mutating one or more amino acids does not reduce the allergenicity of said wheat polypeptide.

5 . The method of claim 2 , wherein said wheat polypeptide is a glutenin or a gliadin.

6 . (canceled)

7 . The method of claim 2 , further comprising identifying an epitope on the wheat polypeptide for the ability to bind a major histocompatibility complex (MHC) class II wherein said predicting is performed prior to said mutating.

8 . (canceled)

9 . The method of claim 2 , further comprising identifying an epitope on the wheat polypeptide from the amino acid sequence of antigen binding regions of T cell receptors (TCRs) which bind to said wheat polypeptide.

10 . (canceled)

11 . The method of claim 1 , wherein said identifying is by computationally predicting the epitope and is optionally performed using a machine-learning algorithm trained to recognize residue pairing preferences on a dataset of MHC II-peptide complexes.

12 . The method of claim 1 , wherein said identifying is by computationally predicting the epitope and is optionally performed using a machine-learning algorithm trained to recognize whether a given MHC II and a given T-cell immunogen are likely to bind each other based on a data set of MHC II-peptide interactions.

13 . The method of claim 9 , wherein said identifying is by computationally predicting the epitope and is performed using an algorithm trained to predict TCR-peptide interactions for peptides derived from said wheat polypeptide.

14 - 17 . (canceled)

18 . The method of claim 2 , wherein said de-epitoped polypeptide binds with a lower affinity to T-cells derived from a celiac patient than a corresponding non-mutated polypeptide binds to T cells derived from said celiac patient and/or said de-epitoped polypeptide activates T-cells derived from a celiac patient to a lesser extent than a corresponding non-mutated polypeptide activates T cells derived from said celiac patient.

19 - 22 . (canceled)

23 . An isolated glutenin or gliadin polypeptide being mutated compared to the corresponding wild-type glutenin or gliadin polypeptide such that it binds with a lower affinity to T-cells derived from a celiac patient than a corresponding non-mutated polypeptide binds to T cells derived from said celiac patient.

24 . An isolated polynucleotide encoding the isolated glutenin or gliadin polypeptide of claim 23 .

25 . An expression vector comprising the isolated polynucleotide of claim 24 , operatively linked to a transcriptional regulatory sequence so as to allow expression of said glutenin or gliadin in a plant cell.

26 . The expression vector of claim 25 , wherein said transcriptional regulatory sequence comprises a plant promoter.

27 . The expression vector of claim 26 , wherein said plant promoter comprises a wheat promoter.

28 . A flour derived from a gluten-free plant, comprising a de-epitoped glutenin or gliadin polypeptide.

29 . The flour of claim 28 , wherein said de-epitoped glutenin or gliadin polypeptide is mutated compared to the corresponding wild-type glutenin or gliadin polypeptide such that it binds with a lower affinity to T-cells derived from a celiac patient than a corresponding non-mutated polypeptide binds to T cells derived from said celiac patient.

30 . A dough comprising the flour of claim 28 .

31 . The dough of claim 30 , characterized by at least one property selected from the group consisting of: a higher development time (DT), a lower stability time (S), a higher degree of softening (DS), a higher consistency (C) value and any combination thereof, as compared to a corresponding dough being absent of the de-epitoped glutenin or gliadin polypeptide.

32 - 35 . (canceled)

36 . A wheat being genetically modified to express the isolated glutenin or gliadin polypeptide of claim 23 .

37 - 45 . (canceled)