PD-1, a receptor for B7-4 for modulating the immune response

摘要

A method for modulating an immune response comprises contacting in vitro a cell expressing B7-4 or an immune cell expressing PD-1 with an agent that modulates the interaction of B74 with PD-1 to thereby modulate the immune response. The agent is selected from an activating antibody that recognizes PD-1 and transmits a negative signal via PD- 1; an antibody that recognizes PD-1 a polypeptide comprising an extra cellular domain of SEQ ID NO:2 or SEQ ID NO:4 in multivalent form; a polypeptide comprising an amino acid sequence encoded by a nucleic aid molecule that hybridizes under stringent conditions to the complement of nucleotides encoding amino acids 19-245 of SEQ ID NO:2 or amino acids 19-238 of SEQ ID NO:4 in multivalent form; an antibody that recognizes PD-1 and doesn't transmit an negative signal, a soluble form of B7-4 and an antibody that recognizes B7-4 and a soluble form of PD-1. Also described is a composition that comprises and antigen and the agent as described above, and a assay for screening for compounds that modulate the binding and/or activity of B7-4 and PD-1. An agent that modulates the interaction off PD-1 and B7-4 such that a negative signal is not transmitted via PD-1 can be used in the manufacture of a medicament for treating a subject having a condition that would benefit from up regulation of a immune response. Preferably the condition is a tumor, a neurological disease or an immunosuppressive disease. An agent that modulates the interaction off PD-1 and B7-4 such that a negative signal is transmitted via PD-1 can be used in the manufacture of a medicament for treating a subject having a condition that would benefit from down regulation of an immune response. Preferably the condition is selected from a transplant, an allergy and an autoimmune disorder.