Variable lymphocyte receptors
View Patent ↗Disclosed are compositions and methods related to variable lymphocyte receptors (VLRs).
1. An isolated polypeptide comprising an N-terminal leucine rich repeat (LRRNT), one or more leucine rich repeats (LRRs), a C-terminal leucine rich repeat (LRRCT), and a connecting peptide, wherein the connecting peptide comprises an alpha helix and wherein the isolated polypeptide is a variable lymphocyte receptor (VLR) or, wherein the VLR selectively binds an antigen and wherein the VLR can function in an adaptive immunity and can be generated by somatic rearrangement.
2. The polypeptide of claim 1 , wherein the connecting peptide is linked to the LRRCT.
3. The polypeptide of claim 1 , further comprising a stalk region and a glycosyl-phosphatidyl-inositol anchor.
4. The polypeptide of claim 3 , further comprising a hydrophobic tail.
5. The polypeptide of claim 3 , wherein the stalk region comprises a threonine-proline rich region.
6. The polypeptide of claim 1 , further comprising a signal peptide.
7. The polypeptide of claim 1 , wherein there are 1-9 LRRs, with LRR1 adjacent to the LRRNT.
8. The polypeptide of claim 7 , wherein LRR1 comprises less than about 20 amino acids.
9. The polypeptide of claim 7 , wherein LRR1 comprises about 18 amino acids.
10. The polypeptide of claim 7 , wherein each of LRR 2-9 comprises less than about 25 amino acids.
11. The polypeptide of claim 1 , wherein the LRRNT comprises less than about 40 amino acids.
12. The polypeptide of claim 11 , wherein the LRRNT comprises the amino acid sequence of SEQ ID NO: 157.
13. The polypeptide of claim 11 , wherein the LRRNT comprises the amino acid sequence of SEQ ID NO: 157 with one or more conservative amino acid substitutions.
14. The polypeptide of claim 1 , wherein the LRRCT comprises less than about 60 amino acids.
15. The polypeptide of claim 14 , wherein the LRRCT comprises the amino acid sequence of SEQ ID NO:158.
16. The polypeptide of claim 14 , wherein the LRRCT comprises the amino acid sequence of SEQ ID NO: 158 with one or more conservative amino acid substitutions.
17. The polypeptide of claim 1 , wherein the connecting peptide comprises less than about 15 amino acids.
18. The polypeptide of claim 1 , wherein the LRRs differ in amino acid sequence from each other and from the LRRNT and the LRRCT.
19. The polypeptide of claim 1 , wherein the polypeptide is about 130 to about 225 amino acids in length.
20. The polypeptide of claim 1 , wherein the antigen is a pathogen.
21. The polypeptide of claim 20 , wherein the pathogen is a bacterium.
22. The polypeptide of claim 1 , wherein the antigen is a toxin.
23. The polypeptide of claim 1 , wherein the polypeptide is bound to a solid support.
24. The polypeptide of claim 23 , wherein the solid support is a mobile solid support.
25. The polypeptide of claim 23 , wherein the solid support is a column.
26. The polypeptide of claim 23 , wherein the solid support is a chip.
27. The polypeptide of claim 23 , wherein the solid support is a multiwell plate.
28. A plurality of the polypeptides of claim 1 , wherein the LRRs are highly variable across polypeptides.
29. The plurality of polypeptides of claim 28 , wherein the plurality is bound to a solid support.
30. The plurality of polypeptide of claim 28 , wherein the solid support is a mobile solid support.
31. The plurality of polypeptide of claim 28 , wherein the solid support is a column.
32. The plurality of polypeptide of claim 28 , wherein the solid support is a chip.
33. The plurality of polypeptide of claim 28 , wherein the solid support is a multiwell plate.