MOLECULAR-CLONING OF A LIGAND FOR THE INDUCIBLE T-CELL GENE 4-1BB - AMEMBER OF AN EMERGING FAMILY OF CYTOKINES WITH HOMOLOGY TO TUMOR-NECROSIS-FACTOR

4-1BB is an inducible T cell antigen that shows sequence homology to m embers of an emerging family of cytokine receptors, including those fo r tumor necrosis factor and nerve growth factor. To aid in the analysi s of the function of 4-1BB we have utilized a soluble form of the mole cule as a probe to identify and clone the gene which encodes its ligan d. The ligand for 4-1BB is a type II membrane glycoprotein that has ho mology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this su perfamily. The gene for 4-1BB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the g ene for CD30. The gene for 4-1BB ligand maps to mouse chromosome 17, b ut considerably distal to the tumor necrosis factor and lymphotoxin ge nes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicke d on similar cell populations stimulated with an antibody to 4-1BB.