T cell inhibitory receptor compositions and uses thereof
The invention relates to compositions which bind T cell inhibitory receptor molecules and modulate T cell activity, and methods of using such compositions. Such compositions include biliary glycoprotein binding agents. Methods for modulating killer T cell activities, including cytotoxicity and proliferation also are provided.
1. A method for suppressing specifically the cytotoxicity or proliferation of killer T cells in a subject, comprising:
administering to a subject in need of such treatment an agent that selectively increases cross-linking of biliary glycoprotein polypeptides, CD66a, on a killer T cell in an amount effective to suppress the activity of killer T cells in the subject, and wherein the agent is an antibody specific for said biliary glycoprotein or an antigen-binding fragment thereof that increases cross-linking of biliary glycoprotein on the killer T cell.
2. The method of claim 1 , wherein the antibody is a monoclonal antibody.
3. The method of claim 1 , wherein the antibody is a chimeric antibody or a humanized antibody.
4. The method of claim 1 , wherein the antibody is a CD66a specific monoclonal antibody.
5. A method for suppressing specifically the cytotoxicity or proliferation of killer T cells in a subject, comprising:
administering to a subject in need of such treatment an agent that selectively increases cross-linking of biliary glycoprotein polypeptides, CD66a, on a killer T cell in an amount effective to suppress the activity of killer T cells in the subject, wherein the agent comprises an isolated ligand for the biliary glycoprotein polypeptide, wherein the ligand binds two or more biliary glycoprotein polypeptides on the killer T cell, and wherein the isolated ligand comprises a biliary glycoprotein polypeptide or fragment thereof.
6. The method of claim 5 , wherein the fragment of biliary glycoprotein is selected from the group consisting of the N-terminal domain of CD66a, NA1B1 domain of CD66a, and the NA1B1A2 domain of CD66a.
7. The method of claim 5 , wherein the biliary glycoprotein polypeptide or the fragment thereof is fused to an immunoglobulin molecule or a fragment thereof.
8. A method for suppressing specifically cytotoxicity or proliferation of killer T cells, comprising:
contacting a population of killer T cells with an agent that selectively increases cross-linking of biliary glycoprotein polypeptides, CD66a, on a killer T cell in an amount effective to suppress the cytotoxicity or proliferation of the killer T cells, and wherein the agent is an antibody specific for said biliary glycoprotein or an antigen-binding fragment thereof that increases cross-linking of biliary glycoprotein on the killer T cell.
9. The method of claim 8 , wherein the antibody is a monoclonal antibody.
10. The method of claim 8 , wherein the antibody is a chimeric antibody or a humanized antibody.
11. The method of claim 8 , wherein the antibody is a CD66a specific monoclonal antibody.
12. A method for suppressing specifically cytotoxicity or proliferation of killer T cells, comprising:
contacting a population of killer T cells with an agent that selectively increases cross-linking of biliary glycoprotein polypeptides, CD66a, on a killer T cell in an amount effective to suppress the cytotoxicity or proliferation of the killer T cells, wherein the agent comprises an isolated ligand for the biliary glycoprotein polypeptide, wherein the isolated ligand binds two or more biliary glycoprotein polypeptides on the killer T cell, and wherein the isolated ligand comprises a soluble biliary glycoprotein molecule or a fragment thereof.
13. The method of claim 12 , wherein the fragment of biliary glycoprotein is selected from the group consisting of the N-terminal domain of CD66a, NA1B1 domain of CD66a, and the NA1B1A2 domain of CD66a.
14. The method of claim 12 , wherein the biliary glycoprotein polypeptide or the fragment thereof is fused to an immunoglobulin molecule or a fragment thereof.