A family of ligands for the TNF receptor superfamily.
Recent progress in the definition of molecules involved in immune regulation has led to the discovery of a number of type I membrane glycoproteins with a distinctive, cysteine-rich, repetitive domain structure within their extracellular regions. Because the prototype members of this family are receptors for cytokines (tumor necrosis factor [TNF] and nerve growth factor [NGF]), it was expected that the ligands for the other receptors would possess cytokine-like activities. This prediction has been fulfilled by the cloning of cDNA encoding a series of type II membrane glycoproteins, with homology to TNF, that bind to, and signal through, their cognate receptors. While the biological role of some of these ligand-receptor pairs remains obscure, at least two members of the family, CD40 and Fas, have proven their importance. The human X-linked immunodeficiency, hyper IgM syndrome, is the result of mutations in the CD40 ligand gene, and the Fas and Fas ligand genes are mutated in two mouse strains, lpr and gld, that develop autoimmune disease. These findings, together with other evidence, point to key roles of CD40/CD40 ligand interactions in immune activation, particularly in T-dependent B cell responses, and of Fas/Fas ligand in apoptosis and peripheral tolerance. These molecules, as well as the other ligands of the family, share the property of costimulation of T cell proliferation and are all expressed by activated T cells. More detailed analysis of the expression patterns of ligands and receptors on lymphocyte subpopulations will be necessary to define their different roles in immune activation and suppression.
Cosman
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Department of Molecular Biology, Immunex Research and Development Corporation, Seattle, Washington 98101.
D000818:Animals; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D053282:CD27 Ligand; D053285:CD30 Ligand; D019013:CD40 Antigens; D023201:CD40 Ligand; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D053222:Fas Ligand Protein; D006801:Humans; D017730:Ki-1 Antigen; D008024:Ligands; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D053259:Lymphotoxin beta Receptor; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008958:Models, Molecular; D005810:Multigene Family; D053278:OX40 Ligand; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D053282:CD27 Ligand; D053285:CD30 Ligand; D019013:CD40 Antigens; C505771:CD70 protein, human; C505772:Cd70 protein, mouse; D018076:DNA, Complementary; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D017730:Ki-1 Antigen; C505697:LTBR protein, human; D008024:Ligands; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053278:OX40 Ligand; D018121:Receptors, Cytokine; D017475:Receptors, Nerve Growth Factor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505714:TNFRSF9 protein, human; C089251:TNFSF4 protein, human; C505774:TNFSF8 protein, human; C505717:Tnfrsf4 protein, mouse; C505715:Tnfrsf9 protein, mouse; C504586:Tnfsf4 protein, mouse; C505775:Tnfsf8 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D023201:CD40 Ligand