The invention relates to a method of testing a compound for biological activity, which method comprises providing cells expressing one of the CD94/NKG2 family of receptors, contacting the cells with recombinant HLA-E under binding conditions in the presence of the test compound, and determining whether the presence of the compound affects the binding of HLA-E to the cells. The HLA-E property of binding to CD94/NKG2 receptors on NK cells and a subset of CD8+ T cells is useful for targeting CD94/NKG2+ cells for a variety of purposes such as identification, isolation, killing or inactivation.
1. A method of testing a compound for biological activity, which method comprises:
(i) providing cells expressing a CD94/NKG2 receptor, wherein the NKG2 member is selected from the group consisting of NKG2A, NKG2B, NKG2C, NKG2E, and NKG2F at the cell surface;
(ii) contacting the cells with HLA-E in the presence of the test compound; and
(iii) determining whether the presence of the compound affects the binding of HLA-E to the cells.
2. The method according to claim 1 , wherein the CD94/NKG2 receptor is an inhibitory NK cell receptor.
3. The method according to claim 1 , wherein the CD94/NKG2 receptor is a stimulatory NK cell receptor.
4. The method according to claim 1 , wherein the NKG2 member is NKG2A.
5. The method according to claim 1 , wherein the NKG2 member is NKG2C.
6. The method according to claim 1 , wherein the NKG2 member is NKG2B.
7. The method according to claim 1 , wherein the NKG2 member is NKG2E.
8. The method according to claim 1 , wherein the NKG2 member is NKG2F.
9. The method of claim 1 , wherein the test compound is an antibody.
10. A method of identifying a compound affecting the binding of HLA-E to CD94/NKG2 receptors, which method comprises:
(i) providing cells expressing a CD94/NKG2 receptor at the cell surface, wherein the NKG2 member is selected from a group consisting of NKG2A, NKG2B, NKG2C, NKG2E, and NKG2F;
(ii) contacting the cells with HLA-E in the presence of a test compound; and
(iii) determining whether the presence of the compound affects the binding of HLA-E to the cells.
11. The method of claim 10 , further comprising using the identified compounds in therapeutic applications, wherein the identified compounds are antibodies.
12. The method of claim 10 , wherein the CD94/NKG2 receptor is an inhibitory NK cell receptor.
13. The method of claim 10 , wherein the CD94/NKG2 receptor is a stimulatory NK cell receptor.
14. The method of claim 10 , wherein the NKG2 member is NKG2A.
15. The method of claim 10 , wherein the NKG2 member is NKG2C.
16. The method of claim 10 , wherein the test compound is an antibody.
17. A method for screening and producing an identified compound which affects the binding of HLA-E to CD94/NKG2 receptors, which method comprises:
(i) selecting a test compound for screening;
(ii) providing cells expressing a CD94/NKG2 receptor at the cell surface, wherein the NKG2 member is selected from a group consisting of NKG2A, NKG2B, NKG2C, NKG2E, and NKG2F;
(iii) contacting the cells with HLA-E in the presence of the test compound;
(iv) determining whether the presence of the test compound affects the binding of HLA-E to the cells thereby providing an identified compound; and
(v) producing the identified compound which affects the binding of HLA-E to the cells.
18. The method of claim 17 , wherein the CD94/NKG2 receptor is an inhibitory NK cell receptor.
19. The method of claim 17 , wherein the CD94/NKG2 receptor is a stimulatory NK cell receptor.
20. The method of claim 17 , wherein the NKG2 member is NKG2A.
21. The method of claim 17 , wherein the NKG2 member is NKG2C.
22. The method of claim 17 , wherein the test compound is an antibody.