Variable lymphocyte receptors, related polypeptides and nucleic acids, and uses thereof
Disclosed are compositions and methods related to variable lymphocyte receptors (VLRs).
1. An isolated nucleic acid that encodes a 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), and 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. An expression vector comprising the nucleic acid of claim 1 operably linked to an expression control sequence.
3. A cultured cell comprising the vector of claim 2 .
4. The nucleic acid of claim 1 , wherein the connecting peptide is linked to the LRRCT.
5. The nucleic acid of claim 1 , wherein the polypeptide further comprises a stalk region and a glycosyl-phosphatidyl-inositol anchor.
6. The nucleic acid of claim 5 , wherein the polypeptide further comprises a hydrophobic tail.
7. The nucleic acid of claim 5 , wherein the stalk region comprises a threonine-proline rich region.
8. The nucleic acid of claim 1 , wherein the polypeptide further comprises a signal peptide.
9. The nucleic acid of claim 1 , wherein the polypeptide comprises 1-9 LRRs, with LRR1 adjacent to LRRNT.
10. The nucleic acid of claim 9 , wherein LRR1 comprises less than 20 amino acids.
11. The nucleic acid of claim 9 , wherein LRR1 comprises about 18 amino acids.
12. The nucleic acid of claim 9 , wherein each of LRR2-9 comprises less than 25 amino acids.
13. The nucleic acid of claim 1 , wherein the LRRNT comprises less than 40 amino acids.
14. The nucleic acid of claim 13 , wherein the LRRNT comprises the amino acid sequence of SEQ ID NO:157.
15. The nucleic acid of claim 13 , wherein the LRRNT comprises the amino acid sequence of SEQ ID NO:157 with one or more conservative amino acid substitutions.
16. The nucleic acid of claim 1 , wherein the LRRCT comprises less than 60 amino acids.
17. The nucleic acid of claim 16 , wherein the LRRCT comprises the amino acid sequence of SEQ ID NO:158.
18. The nucleic acid of claim 16 , wherein the LRRCT comprises the amino acid sequence of SEQ ID NO:158 with one or more conservative amino acid substitutions.
19. The nucleic acid of claim 1 , wherein the connecting peptide comprises less than 15 amino acids.
20. The nucleic acid of claim 1 , wherein the LRRs differ in amino acid sequence from each other and from the LRRNT and the LRRCT.
21. The nucleic acid of claim 1 , wherein the polypeptide is about 130 to about 225 amino acids in length.
22. The nucleic acid of claim 1 , wherein the antigen is a pathogen.
23. The nucleic acid of claim 22 , wherein the pathogen is a bacterium.
24. The nucleic acid of claim 1 , wherein the antigen is a toxin.