Peptides for use in treatment and diagnosis of type 1 diabetes

Abstract

Provided herein are compositions and methods for treating autoimmune diabetes such as type 1 diabetes (T1D), diagnosing autoimmune diabetes such as T1D, assessing treatment efficacy, and selecting subjects for treatment, e.g., using a peptide or epitope disclosed.

1 . A composition, comprising at least one peptide, the at least one peptide comprising at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), PKAARPPVTPVLLEKKS (SEQ ID NO: 13), or at least one T cell epitope contained within the at least one amino acid sequence. 
     
     
         2 . The composition of  claim 1 , comprising at least two peptides, wherein
 a first peptide comprises at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), PKAARPPVTPVLLEKKS (SEQ ID NO: 13), or at least one T cell epitope contained within the at least one amino acid sequence; and   a second peptide comprises at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), PKAARPPVTPVLLEKKS (SEQ ID NO: 13), or at least one T cell epitope contained within the at least one amino acid sequence.   
     
     
         3 . The composition of  claim 1 , comprising at least three peptides, wherein
 a first peptide comprises at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), PKAARPPVTPVLLEKKS (SEQ ID NO: 13), or at least one T cell epitope contained within the at least one amino acid sequence;   a second peptide comprises at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), PKAARPPVTPVLLEKKS (SEQ ID NO: 13), or at least one T cell epitope contained within the at least one amino acid sequence; and   a third peptide comprises at least one amino acid sequence selected from PLLALLALWGPDP (SEQ ID NO: 1), PKTRREAEVGQ (SEQ ID NO: 2), RREAEDLQGSL (SEQ ID NO: 3), RREAEDLEGSL (SEQ ID NO: 4), DLQVGQVELGGGP (SEQ ID NO: 5), DLQVGEVELGGGP (SEQ ID NO: 6), CGSHLVEALYLVC (SEQ ID NO: 7), MNILLEYVVKS (SEQ ID NO: 8), NMFTYEIAPVFVLLEYV (SEQ ID NO: 9), NVCFWYIPPSLRTLEDN (SEQ ID NO: 10), FNQLSTGLDMVGLAADW (SEQ ID NO: 11), GRTGTYILIDMVLNRMA (SEQ ID NO: 12), PKAARPPVTPVLLEKKS (SEQ ID NO: 13), or at least one T cell epitope contained within the at least one amino acid sequence.   
     
     
         4 . The composition of  claim 1 , wherein the at least one T cell epitope comprises an amino acid sequence LLALLALWGPD (SEQ ID NO: 14). 
     
     
         5 . The composition of  claim 1 , wherein the at least one T cell epitope is not a CD8+ T cell epitope. 
     
     
         6 . The composition of  claim 1 , wherein at least one of the peptides comprises a modification on the N-terminus and/or C-terminus. 
     
     
         7 . The composition of  claim 6 , wherein at least one of the peptides comprises an N-terminal pyroglutamate or acetyl group and/or a C-terminal amide group. 
     
     
         8 . The composition of  claim 7 , wherein each of the peptides comprises an N-terminal pyroglutamate or acetyl group and/or a C-terminal amide group. 
     
     
         9 . The composition of  claim 1 , wherein each of the peptides is independently between 8 to 50 amino acids in length. 
     
     
         10 . The composition of  claim 9 , wherein each of the peptides is independently between 8 to 30 amino acids in length. 
     
     
         11 . The composition of  claim 10 , wherein each of the peptides is independently between 8 to 20 amino acids in length. 
     
     
         12 - 17 . (canceled) 
     
     
         18 . A composition comprising one or more polynucleotides encoding the peptides of the composition of  claim 1 . 
     
     
         19 . An isolated antigen presenting cell comprising the composition of  claim 1 . 
     
     
         20 . A kit comprising the composition of  claim 1  and at least one means to detect binding of one or more of the peptides in the composition to T cells. 
     
     
         21 - 24 . (canceled) 
     
     
         25 . A method for treating type 1 diabetes (T1D) in a subject, the method comprising:
 administering to a subject having or suspected of having T1D an effective amount of a composition of  claim 1 .   
     
     
         26 . A method for identifying a subject as having or at risk of T1D, the method comprising:
 determining a T cell response to a composition of  claim 1  in a sample comprising a T cell from the subject; and assessing whether or not the subject has or is at risk of having T1D.   
     
     
         27 - 37 . (canceled) 
     
     
         38 . The method of  claim 26 , wherein the method further comprises treating the subject if identified as having or at risk of having T1D or providing information to the subject about a treatment. 
     
     
         39 . A method for assessing the efficacy of treatment of Type I Diabetes in a subject, the method comprising:
 (a) measuring a T cell response to a composition of  claim 1  in sample from a subject that has been administered a tolerogenic treatment; and   (b) assessing the efficacy based on the measuring.   
     
     
         40 . The method of  claim 39 , further comprising:
 (c) treating the subject, or suggesting a treatment to the subject, based on the assessing.   
     
     
         41 - 52 . (canceled) 
     
     
         53 . A method for selecting a subject having Type I Diabetes for treatment, the method comprising:
 (a) measuring a T cell response to a composition of  claim 1  in a sample from a subject having Type I Diabetes; and   (b) treating the subject, or suggesting a treatment to the subject if the T cell response is at or above a control T cell response.   
     
     
         54 - 62 . (canceled)