Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor.
The human OX-40 cell surface antigen is a CD4+ T cell activation marker that acts as a costimulatory receptor and is a member of the nerve growth factor receptor/tumor necrosis factor (TNF) receptor family. Using a soluble form of the receptor, the extracellular region fused with human immunoglobulin Fc, we expression cloned the human OX-40 ligand cDNA from a library derived from an activated B lymphoblastoid cell line MSAB. The encoded protein is identified as gp34, a type II transmembrane antigen previously known to be expressed only by human T cell lymphotropic virus 1-infected cells. We describe gp34 as a new member of the TNF family, and find that the recombinant ligand expressed in COS cells costimulates phorbol myristate acetate, phytohemagglutinin, and anti-CD3-induced CD4+ T cell proliferation.
Godfrey
W R
WR
Department of Pathology, Stanford University School of Medicine, California 94305.
Fagnoni
F F
FF
Harara
M A
MA
Buck
D
D
Engleman
E G
EG
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011961:Receptors, Fc / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000737:chemistry* / Q000276:immunology
D000954:Antigens, Surface; D008024:Ligands; D008565:Membrane Proteins; D011961:Receptors, Fc; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D004247:DNA