TR2 (TNFR-related 2, HVEM, or TNFRSF-14), a member of the TNFR family, is involved in a number of immune responses. While TR2 is expressed on the surface of T cells during the resting state, little is known regarding how expression of the TR2 gene is regulated. To understand the mechanisms regulating the expression of TR2 in T cells, we analyzed the 5' flanking region of TR2. We identified all important region for the activity of the TR2 promoter using site directed mutagenesis. Using EMSA analysis, we found that IRF-2 was bound to the promoter region of the TR2 gene during the resting state of EL-4 T cells. Transfection of IRF-2 expression plasmid and of dominant negative IRF-2 mutant further confirmed our results. Together, these data demonstrate that IRF-2 is involved in the regulation of TR2 expression in EL-4 T cells. (c) 2007 Elsevier Inc. All rights reserved.