title: Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor.
abstract: 4-1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4-1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4-1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. 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 gene for CD30. The gene for 4-1BB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB.
authors.affiliation: Immunex Research and Development Corporation, Seattle, WA 98101.
authors.forename: R G
authors.initials: RG
authors.lastname: Goodwin
authors.forename: W S
authors.initials: WS
authors.lastname: Din
authors.forename: T
authors.initials: T
authors.lastname: Davis-Smith
authors.forename: D M
authors.initials: DM
authors.lastname: Anderson
authors.forename: S D
authors.initials: SD
authors.lastname: Gimpel
authors.forename: T A
authors.initials: TA
authors.lastname: Sato
authors.forename: C R
authors.initials: CR
authors.lastname: Maliszewski
authors.forename: C I
authors.initials: CI
authors.lastname: Brannan
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
mesh_terms: D053330:4-1BB Ligand; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009115:Muridae; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D053330:4-1BB Ligand; D016207:Cytokines; D018076:DNA, Complementary; D008024:Ligands; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C505974:TNFSF9 protein, human; C505975:Tnfsf9 protein, mouse; D014409:Tumor Necrosis Factor-alpha