A NEWLY IDENTIFIED MEMBER OF THE TUMOR-NECROSIS-FACTOR RECEPTOR SUPERFAMILY WITH A WIDE TISSUE DISTRIBUTION AND INVOLVEMENT IN LYMPHOCYTE-ACTIVATION

The tumor necrosis factor receptor (TNFR) superfamily consists of appr oximately 10 characterized members of human proteins. We have identifi ed a new member of the TNFR superfamily, TR2, from a search of an expr essed sequence tag data base, cDNA cloning and Northern blot hybridiza tion demonstrated multiple mRNA species, of which a 1.7-kilobase form was most abundant. However, TR2 is encoded by a single gene which, map s to chromosome 1p36.22-36.3, in the same region as several other memb ers of the TNFR superfamily. The most abundant TR2 open reading frame encodes a 283-amino acid single transmembrane protein with a 36-residu e signal sequence, two perfect and two imperfect TNFR-like cysteine-ri ch domains, and a short cytoplasmic tail with some similarity to 4-1BB and CD40. TR2 mRNA is expressed in multiple human tissues and cell li nes and shows a constitutive and relatively high expression in periphe ral blood T cells, B cells, and monocytes. A TR2-Fc fusion protein inh ibited a mixed lymphocyte reaction-mediated proliferation suggesting t hat the receptor and/or its ligand play a role in T cell stimulation.