The invention provides methods for modulating an immune response comprising contacting an immune cell with an agent that modulates BTF4 or B7-L1 mediated signaling. BTF4 or B7-L1 mediated signaling may either be increased, to thereby downregulate the immune response, or alternatively may be decreased, to upregulate the immune response. Modulation may be either activation or inhibition, and contacting may occur in vivo or in vitro. Performance of this method in vivo is also potentially therapeutic for an individual who may benefit from the upregulation or downregulation of an immune response. Such modulation to downregulate the immune response serves as a therapeutic e.g., for an individual who has received an organ transplant, or has a condition such as an allergy, or an autoimmune disorder. Alternatively, modulation to upregulate the immune response serves as a therapeutic for an individual, e.g., who has a condition such as an immunosuppressive disorder or a tumor. Methods for identifying an agent that modulates BTF4 signaling or B7-L1 signaling is also provided.