Patent ID: 7432059

Claim:
A method of identifying a compound which upmodulates T cell activation at both a low and high antigen concentration comprising: a) contacting a T cell expressing PD-1 with a test compound at a low concentration of antigen to which the T cell is specific in the presence of a costimulatory signal and a PD-1 ligand having the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:5, wherein the low concentration of antigen is minimally sufficient to induce T cell proliferation to levels above background in the absence of a PD-1-mediated signal and wherein the low concentration of antigen is 0.001 μg/ml−0.01 μg/ml; b) determining the ability of the test compound to upmodulate T cell proliferation or cytokine production at the low antigen concentration; c) contacting a T cell expressing PD-1 with the test compound at a high antigen concentration in the presence of a costimulatory signal and a PD-1 ligand having the amino acid sequence selected from the group consisting of SEQ ID NO:2 or SEQ ID NO:5, wherein the high antigen concentration is 0.1 μg/ml−1.0 μg/ml; and d) determining the ability of the test compound to upmodulate T cell proliferation or cytokine production at the high antigen concentration, wherein the ability of the compound to upmodulate T cell proliferation or cytokine production at both the low and high antigen concentration identifies the compound as one that upmodulates T cell activation at a both a low and high antigen concentration.