HLA-E BINDING
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 . An in vitro method of protecting a cell or inhibiting HLA-E mediated inhibition of NK cell activity comprising:
(a) selecting an antibody that interferes with HLA-E-binding to an inhibitory CD94/NKG2 receptor from the group consisting of an anti-CD94 antibody, an anti-NKG2A antibody and an anti-HLA-E antibody; and
(b) contacting an NK or T cell expressing an inhibitory CD94/NKG2 receptor with the antibody in vitro.
2 . The method of claim 1 , wherein the inhibitory CD94/NKG2-receptor is NKG2A.
3 . The method of claim 1 , wherein the antibody is an anti-CD94 antibody.
4 . The method of claim 1 , wherein the antibody is an anti-NKG2A antibody.
5 . The method of claim 1 , wherein the antibody is an anti-HLA-E antibody.
6 . The method of claim 1 , wherein the compound is a multimer of HLA-E comprising two or more HLA-E molecules.
7 . The method of claim 6 , wherein the multimer has an enhanced binding capability compared to non-multimeric HLA-E.
8 . The method of claim 6 , wherein the multimer comprises recombinant soluble HLA-E molecules.
9 . The method of claim 8 , wherein the recombinant soluble HLA-E molecules are attached via a linker molecule.
10 . An in vitro method of preventing HLA-E medicated inhibition of NK cell activity, said method comprising:
(a) selecting an anti-NKG2A antibody; and
(b) contacting an NK or T cell expressing an inhibitory CD94/NKG2 receptor with the anti-NKG2A antibody in vitro.
11 . A transgenic animal comprising a recombinant DNA encoding HLA-E having an HLA-B8 leader sequence.