HERPESVIRUS ENTRY MEDIATOR LIGAND (HVEM-L), A NOVEL LIGAND FOR HVEM TR2, STIMULATES PROLIFERATION OF T-CELLS AND INHIBITS HT29 CELL-GROWTH/

Herpesvirus entry mediator (HVEM), a member of the tumor necrosis fact or (TNF) receptor family, mediates herpesvirus entry into cells during infection. Upon overexpression, HVEM activates NF-kappa B and AP-1 th rough a TNF receptor-associated factor (TRAF)-mediated mechanism. Usin g an HVEM-Fc fusion protein, we screened soluble forms of novel TNF-re lated proteins derived from an expressed sequence fag data base. One o f these, which we designated HVEM-L, specifically bound to HVEM-Fc wit h an affinity of 44 nM. This association was confirmed with soluble an d membrane forms of both receptor and ligand, HVEM-L mRNA is expressed in spleen, lymph nodes, macrophages, and T cells and encodes a 240-am ino acid protein. A soluble, secreted form of the protein stimulates p roliferation of T lymphocytes during allogeneic responses, inhibits HT -29 cell growth, and weakly stimulates NF-kappa B-dependent transcript ion.