NOVEL PEPTIDES THAT BIND TO TYPES OF MHC CLASS II AND THEIR USE ON DIAGNOSIS AND TREATMENT
It is provided novel peptides from human alpha-enolase, collagen type II and vimentin that bind to types of MHC class II that is associated with rheumatoid arthritis. There is also provided novel therapies and methods for diagnosis of rheumatoid arthritis.
1 . A synthesized or recombinantly produced peptide of between 8 and 20 amino acids comprising at least 8 consecutive amino acids residues with a sequence present in one of SEQ ID NO 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 30, 31, 32, 34, 35, 36, 38, 39, 40, 41, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 69, 72, 73, 74, 75, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87.
2 . The synthesized or recombinantly produced peptide according to claim 1 consisting of a sequence selected from SEQ ID NO 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 30, 31, 32, 34, 35, 36, 38, 39, 40, 41, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 69, 72, 73, 74, 75, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87.
3 . The synthesized or recombinantly produced peptide according to claim 1 wherein the sequence is selected from SEQ ID NO 11, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 34.
4 . The synthesized peptide according to claim 1 wherein the sequence is selected from SEQ ID NO 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 30, 31, 36, 45, 46, 47, 48 and SEQ ID NO 72, 73, 74, 75, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87 and where said peptide comprises at least one citrulline residue.
5 . The synthesized or recombinantly produced peptide according to claim 1 where the sequence is selected from SEQ ID NO 1, 2, 3, 4, 5, 6, 7, 8, 10, 1 1, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23 24, 32, 34, 35 and 36.
6 . The synthesized peptide according to claim 5 wherein the sequence is selected from SEQ ID NO 15, 16, 17, 18, 19, 20, 21, 22, 23, and 36, said peptide comprising at least one citrulline residue.
7 . The synthesized or recombinantly produced peptide according to claim 1 where the sequence is selected from SEQ ID NO 25, 26, 27, 30, 31, 38, 39, 40, 41, 43, 45, 46, 47 and 48.
8 . The synthesized peptide according to claim 7 wherein the sequence is selected from SEQ ID NO 30, 31, 45, 46, 47 and 48, said peptide comprising at least one citrulline residue.
9 . The synthesized or recombinantly produced peptide according to claim 1 where the sequence is selected from SEQ ID NO 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 69, 72, 73, 74, 75, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87.
10 . The synthesized peptide according to claim 9 wherein the sequence is selected from SEQ ID NO 72, 73, 74, 75, 78, 79, 80, 81, 82, 83, 84, 85, 86, and 87, said peptide comprising at least one citrulline residue.
11 . A complex of the peptide according to claim 1 and a human recombinant MHC class II protein.
12 . (canceled)
13 . (canceled)
14 . A method for diagnosis of rheumatoid arthritis comprising the steps of
1) obtaining a sample of T-cells from a patient,
2) contacting the sample comprising T-cells with the synthesized or recombinantly produced peptide according to any one of claims 1 to 10 or the peptide-MHC complex according to claim 11 , and
3) detecting the ability of the T-cells to become activated by the peptide or peptide-MHC complexes.
15 . A kit of parts comprising the synthesized or recombinantly produced peptide according to claim 1 .
16 . The kit according to claim 15 additionally comprising at least one cell culture vessel.
17 . The kit according to claim 15 comprising means for detecting the expression of at least one protein selected from the group consisting of CD3, CD4, Foxp3, CD25, TNF alpha, Interferon gamma, interleukin-17A, interleukin-17F, CD154, CD69, Ki 67, interleukin-2, interleukin-13 and interleukin-10.
18 . The kit according to claim 17 where the means for detection is an antibody against said protein.
19 . The kit according to claim 17 where the means for detection is a set of primers for RT-PCR.
20 . (canceled)
21 . (canceled)
22 . A method for treatment of rheumatoid arthritis comprising administering to a patient a peptide of between 8 and 20 amino acids comprising at least 8 consecutive amino acid residues with a sequence present in a sequence selected from SEQ ID NO 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87, or a complex of such a peptide and a human recombinant MHC class II protein or peptide that consists of a sequence selected from one of SEQ ID NO 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87.
23 . A pharmaceutical composition comprising a peptide of between 8 and 20 amino acids comprising at least 8 consecutive amino acid residues with a sequence present in a sequence selected from SEQ ID NO 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87, or a complex of such a peptide and a human recombinant MHC class II protein or peptide that consists of a sequence selected from one of SEQ ID NO 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86 and 87 and a pharmaceutically suitable additive.