Antibodies to toll-like receptor-2
It has been found that Toll-like receptor 1 and Toll-like receptor 2 (TLR2) physically interact. Antibodies that specifically bind to TLR2 and selectively inhibit induction of cytokines are also described. The invention relates to specific antibodies that selectively bind to TLR2, and to methods of identifying compounds that selectively interfere with signaling through TLR1/TLR2 complexes.
1. An isolated antibody or antigen-binding fragment thereof that competes with 11 G7 antibody for specifically binding to the extracellular domain of human Toll-like receptor-2 protein (TLR2), wherein the antibody blocks cytokine production by human peripheral blood mononuclear cells (PBMCs) stimulated with ara-lipoarabinomannan (araLAM), but does not block cytokine production by PBMCs stimulated with zymosan.
2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof inhibits binding of TLR1 to TLR2, but not binding of TLR2 to TLR6.
3. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof inhibits ligand binding to TLR1/TLR2, but not to TLR2/TLR6.
4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a monoclonal antibody.
5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is selected from the group consisting of a chimeric antibody, a recombinant antibody, a humanized antibody, and a single-chain antibody.
6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody competes with an antibody produced by a hybridoma cell line deposited with the American Type Culture Collection under deposit no. PAT-5014 for binding to the extracellular domain of TLR2.
7. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody selectively binds to an antigen that is selectively bound by an antibody produced by a hybridoma cell line deposited with the American Type Culture Collection under deposit no. PAT-5014.
8. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is produced by immunizing an animal with a cell expressing TLR2.
9. A cell line that produces the antibody of claim 1 .
10. The cell line of claim 9 , wherein the cell line is a mouse hybridoma cell line.
11. A method of inhibiting TLR2 activation in a cell, the method comprising contacting the cell with the antibody of claim 1 .
12. A pharmaceutical composition comprising the antibody of claim 1 .
13. A method of decreasing inflammation in a subject, the method comprising administering to the subject the pharmaceutical composition of claim 12 .
14. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antigen-binding fragment thereof comprises a Fab fragment.
15. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antigen-binding fragment thereof comprises a single chain antibody.
16. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is chimeric.
17. A hybridoma cell line that produces the chimeric antibody or antigen-binding fragment thereof of claim 16 .
18. The antibody or antigen-binding fragment thereof of claim 1 wherein the antibody or antigen-binding fragment thereof is humanized.
19. A hybridoma cell line that produces the humanized antibody of claim 18 .