Abstract: The invention provides methods (also referred to herein as a “screening assays”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) capable of modulating tolerance. In one embodiment, the invention provides methods for identifying a tolerance modulatory compound, comprising, e.g., contacting a T cell with a stimulating agent and a test compound and assaying for expression or activity of at least one T regulatory (Treg) marker and at least one T effector (Teff) marker.