Immunogenic CD1d binding peptides
The invention relates to isolated immunogenic peptides comprising a CD1d binding peptide, and immediately adjacent or separated from said CD1d binding peptide, a redox motif sequence which is further flanked by a histidine or tryptophan amino acids. The invention further relates to these peptides for use as a medicament The invention further relates to methods wherein these peptides are used for generating NKT cells which are cytolytic against cells presenting the cognate antigen.
1. An isolated fusion peptide of between 12 and 100 amino acids comprising
(i) a first peptide of an antigen comprising the [FWYH]-X(2)-[VILM]-X(2)-[FWYH] (SEQ ID NO: 61) first sequence motif, wherein the antigen is myelin oligodendrocyte glycoprotein (MOG), and
(ii) a [HW]-X(0,2)-C-X(2)-C ((SEQ ID NO: 7), (SEQ ID NO: 8), (SEQ ID NO: 9)) or C-X(2)-C-X(0,2)-[HW] ((SEQ ID NO: 10), (SEQ ID NO: 11), (SEQ ID NO: 12)) redox motif sequence, which is immediately adjacent or separated by at most 7 amino acids from said first sequence motif,
wherein the redox motif sequence is located N terminally from the first sequence motif within the fusion peptide.
2. The fusion peptide of claim 1 , wherein said fusion peptide has a length of between 12 and 50 amino acids.
3. The fusion peptide of claim 1 , wherein the redox motif sequence is [HW]-C-X(2)-C (SEQ ID NO: 7) or C-X(2)-C-[HW] (SEQ ID NO: 10).
4. The fusion peptide of claim 1 , wherein the redox motif sequence is H-C-X(2)-C (SEQ ID NO: 48) or C-X(2)-C-H (SEQ ID NO: 42).
5. The fusion peptide of claim 1 , wherein said first peptide comprises the amino acid sequence of FLRVPCWKI (SEQ ID NO: 103).
6. The fusion peptide of claim 1 , wherein said fusion peptide comprises the sequence of HCGPCGGFLRVPCWKI (SEQ ID NO: 87), WCGPCGGFLRVPCWKI (SEQ ID NO: 88), HCHGCGGFLRVPCWKI (SEQ ID NO: 105), or WCHGC GG FLRVPCWKI (SEQ ID NO: 106).
7. A method for preparing a peptide comprising the step of:
identifying within an antigen a sequence comprising the [FWYH]-X(2)-[VILM]-X(2)-[FWYH] (SEQ ID NO: 61) first sequence motif, wherein the antigen is myelin oligodendrocyte glycoprotein (MOG); and
preparing a peptide of between 12 and 100 amino comprising the first sequence motif and immediately adjacent or separated by at most 7 amino acids therefrom a [HW]-X(0,2)-C-X(2)-C ((SEQ ID NO: 7), (SEQ ID NO: 8), (SEQ ID NO: 9)) or C-X(2)-C-X(0,2)-[HW] ((SEQ ID NO: 10), (SEQ ID NO: 11), (SEQ ID NO: 12)) redox motif sequence, wherein the redox motif sequence is located N terminally from the first sequence motif within the fusion peptide.
8. The fusion peptide of claim 1 , wherein the redox motif is [HW]-X(0,2)-C-X(2)-C ((SEQ ID NO: 7), (SEQ ID NO: 8), (SEQ ID NO: 9)).
9. The fusion peptide of claim 1 , wherein the redox motif is [HW]-C-X(2)-C (SEQ ID NO: 7).
10. The fusion peptide of claim 1 , wherein the redox motif is H-C-X(2)-C (SEQ ID NO: 48).
11. The fusion peptide of claim 1 , wherein the first sequence motif is [FWY]-X(2)-[VILM]-X(2)-[FWY] (SEQ ID NO: 63).
12. The fusion peptide of claim 11 , wherein the redox motif is [HW]-X(0,2)-C-X(2)-C ((SEQ ID NO: 7), (SEQ ID NO: 8), (SEQ ID NO: 9)).
13. The fusion peptide of claim 11 , wherein the redox motif is [HW]-C-X(2)-C (SEQ ID NO: 7).
14. The fusion peptide of claim 11 , wherein the redox motif is H-C-X(2)-C (SEQ ID NO: 48).
15. The fusion peptide of claim 5 , wherein the redox motif is [HW]-X(0,2)-C-X(2)-C ((SEQ ID NO: 7), (SEQ ID NO: 8), (SEQ ID NO: 9)).
16. The fusion peptide of claim 5 , wherein the redox motif is [HW]-C-X(2)-C (SEQ ID NO: 7).
17. The fusion peptide of claim 5 , wherein the redox motif is H-C-X(2)-C (SEQ ID NO: 48).
18. An isolated fusion peptide of between 12 and 100 amino acids comprising
(i) a first peptide of an antigen comprising the [FWYH]-X(2)-[VILM]-X(2)-[FWYH] (SEQ ID NO: 61) first sequence motif, wherein the antigen is myelin oligodendrocyte glycoprotein (MOG), and
(ii) a [HW]-C-X(2)-C (SEQ ID NO: 7) or C-X(2)-C-[HW] (SEQ ID NO: 10) redox motif sequence, which is immediately adjacent or separated by at most 7 amino acids from said first sequence motif,
wherein the redox motif sequence is located C terminally from the first sequence motif within the fusion peptide.
19. The fusion peptide of claim 5 , wherein the redox motif is H-C-X(2)-C (SEQ ID NO: 48) or C-X(2)-C-H (SEQ ID NO: 42).