Molecular characterization of murine and human OX40/OX40 ligand systems

Identification of a human OX40 ligand as the HTLV-1-regulated protein gp34

Peter R. Baum, Richard B. Gayle, Fred Ramsdell, Subhashini Srinivasan, Rick A. Sorensen, Mark L. Watson, Michael F Seldin, Elizabeth Baker, Grant R. Sutherland, Ky N. Clifford, Mark R. Alderson, Ray G. Goodwin, William C. Fanslow

Research output: Contribution to journalArticle

246 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3992-4001
Number of pages10
JournalEMBO Journal
Volume13
Issue number17
StatePublished - 1994
Externally publishedYes

Fingerprint

OX40 Ligand
Human T-lymphotropic virus 1
T-cells
Identification (control systems)
Ligands
Genes
Proteins
T-Lymphocytes
OX40 Receptor
pX Genes
T-Cell Lymphoma
Tumor Necrosis Factor Receptors
Chromosome Mapping
Chromosomes, Human, Pair 1
Cell proliferation
Human Genome
Chromosomes
Taxation
Gene Library
Interleukin-4

Keywords

  • HTLV-1
  • Ligand
  • Receptor
  • T cell (lymphocytes)
  • TNF

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Baum, P. R., Gayle, R. B., Ramsdell, F., Srinivasan, S., Sorensen, R. A., Watson, M. L., ... Fanslow, W. C. (1994). Molecular characterization of murine and human OX40/OX40 ligand systems: Identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. EMBO Journal, 13(17), 3992-4001.

Molecular characterization of murine and human OX40/OX40 ligand systems : Identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. / Baum, Peter R.; Gayle, Richard B.; Ramsdell, Fred; Srinivasan, Subhashini; Sorensen, Rick A.; Watson, Mark L.; Seldin, Michael F; Baker, Elizabeth; Sutherland, Grant R.; Clifford, Ky N.; Alderson, Mark R.; Goodwin, Ray G.; Fanslow, William C.

In: EMBO Journal, Vol. 13, No. 17, 1994, p. 3992-4001.

Research output: Contribution to journalArticle

Baum, PR, Gayle, RB, Ramsdell, F, Srinivasan, S, Sorensen, RA, Watson, ML, Seldin, MF, Baker, E, Sutherland, GR, Clifford, KN, Alderson, MR, Goodwin, RG & Fanslow, WC 1994, 'Molecular characterization of murine and human OX40/OX40 ligand systems: Identification of a human OX40 ligand as the HTLV-1-regulated protein gp34', EMBO Journal, vol. 13, no. 17, pp. 3992-4001.
Baum, Peter R. ; Gayle, Richard B. ; Ramsdell, Fred ; Srinivasan, Subhashini ; Sorensen, Rick A. ; Watson, Mark L. ; Seldin, Michael F ; Baker, Elizabeth ; Sutherland, Grant R. ; Clifford, Ky N. ; Alderson, Mark R. ; Goodwin, Ray G. ; Fanslow, William C. / Molecular characterization of murine and human OX40/OX40 ligand systems : Identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. In: EMBO Journal. 1994 ; Vol. 13, No. 17. pp. 3992-4001.
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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.",
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AU - Sorensen, Rick A.

AU - Watson, Mark L.

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