Screening for modulators of PSGL-1 with respect to T cell or NK cell death
Compounds that bind to P-Selectin Glycoprotein 1 (PSGL-1) on the surface of T cells or natural killer (NK) cells can be used to induce T cell or NK cell depletion and/or to induce T cell or NK cell apoptosis. The compounds and methods of the invention can be used to control unwanted T cell- or NK cell-mediated immune responses in conditions such as autoimmune diseases, transplant rejection, and allergic diseases.
1. A method of screening for a modulator of P-Selectin Glycoprotein Ligand-1 (PSGL-1) function with respect to T cell or NK cell death, the method comprising:
providing a T cell or a NK cell expressing PSGL-1 on its surface;
contacting the cell with a test substance;
measuring the cell death of the T cell or NK cell after the contacting; and
determining the test substance is a modulator of PSGL-1 function when the cell death is increased compared to a control without the contacting.
2. The method of claim 1 , wherein the test substance is an antibody or antigen binding fragment thereof that specifically binds to PSGL-1.
3. The method of claim 1 , wherein the test substance is a monoclonal antibody that specifically binds to PSGL-1.
4. The method of claim 3 , further comprising contacting the monoclonal antibody with an agent that binds to the monoclonal antibody and induces cross-linking of a plurality of PSGL-1 antigens on the surface of the cell.
5. The method of claim 1 , wherein the method comprises inducing cross-linking of a plurality of PSGL-1 antigens on the surface of the cell, wherein the cross-linking induces a signal transduction pathway that results in death of the cell.
6. The method of claim 1 , wherein the cell is an activated T cell.
7. The method of claim 1 , wherein the cell is a CD4 + T cell.
8. The method of claim 1 , wherein the cell is a CD8 + T cell.
9. The method of claim 1 , wherein the cell is a NK cell.