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PMID: 8076595 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34.

The EMBO journal ·Vol. 13 ·No. 17 ·1994-09-01 ·Pages 3992-4001

Baum PR, Gayle RB, Ramsdell F, Srinivasan S, Sorensen RA, Watson ML, Seldin MF, Baker E, Sutherland GR, Clifford KN

Abstract

A ligand was cloned for murine OX40, a member of the TNF receptor family, using a T cell lymphoma cDNA library. The ligand (muOX40L) is a type II membrane protein with significant identity to human gp34 (gp34), a protein whose expression on HTLV-1-infected human leukemic T cells is regulated by the tax gene. The predicted structures of muOX40L and gp34 are similar to, but more compact than, those of other ligands of the TNF family. Mapping of the muOX40L gene revealed tight linkage to gld, the FasL gene, on chromosome 1. gp34 maps to a homologous region in the human genome, 1q25. cDNAs for human OX40 receptor were cloned by cross-hybridization with muOX40, and gp34 was found to bind the expressed human receptor. Lymphoid expression of muOX40L was detected on activated T cells, with higher levels found on CD4+ rather than CD8+ cells. The cell-bound recombinant ligands are biologically active, co-stimulating T cell proliferation and cytokine production. Strong induction of IL-4 secretion by muOX40L suggests that this ligand may play a role in regulating immune responses. In addition, the HTLV-1 regulation of gp34 suggests a possible connection between virally induced pathogenesis and the OX40 system.

MeSH Terms
Amino Acid Sequence Animals Antigens, Surface Base Sequence Chromosome Mapping Chromosomes, Human, Pair 1 Cloning, Molecular Cytokines/biosynthesis Female Gene Expression Regulation Human T-lymphotropic virus 1/metabolism Humans Ligands Membrane Glycoproteins Membrane Proteins Mice Mice, Inbred C57BL Models, Molecular Molecular Sequence Data OX40 Ligand Receptors, OX40 Receptors, Tumor Necrosis Factor/genetics,metabolism Recombinant Fusion Proteins/metabolism Sequence Homology, Amino Acid T-Lymphocytes/metabolism Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics,metabolism Tumor Necrosis Factor-alpha/genetics,metabolism Tumor Necrosis Factors
Chemicals
Antigens, Surface Cytokines Ligands Membrane Glycoproteins Membrane Proteins OX40 Ligand Receptors, OX40 Receptors, Tumor Necrosis Factor Recombinant Fusion Proteins TNFRSF4 protein, human TNFSF4 protein, human Tnfrsf4 protein, mouse Tnfsf4 protein, mouse Tumor Necrosis Factor Receptor Superfamily, Member 7 Tumor Necrosis Factor-alpha Tumor Necrosis Factors
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Baum P R
Department of Gene Expression, Immunex R&D Corporation, Seattle, WA 98101.
Gayle R B
Ramsdell F
Srinivasan S
Sorensen R A
Watson M L
Seldin M F
Baker E
Sutherland G R
Clifford K N
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-09-01
Pages
3992-4001
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395319
Subset
IM
Grants
NIAMS NIH HHS · AR41053 · United States
Databases
GENBANK
U12763
External Links
PubMed source PMC Full Text View journal details
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