Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth.
Herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor family, mediates herpesvirus entry into cells during infection. Upon overexpression, HVEM activates NF-kappaB and AP-1 through a TNF receptor-associated factor (TRAF)-mediated mechanism. Using an HVEM-Fc fusion protein, we screened soluble forms of novel TNF-related proteins derived from an expressed sequence tag data base. One of these, which we designated HVEM-L, specifically bound to HVEM-Fc with an affinity of 44 nM. This association was confirmed with soluble and membrane forms of both receptor and ligand. HVEM-L mRNA is expressed in spleen, lymph nodes, macrophages, and T cells and encodes a 240-amino acid protein. A soluble, secreted form of the protein stimulates proliferation of T lymphocytes during allogeneic responses, inhibits HT-29 cell growth, and weakly stimulates NF-kappaB-dependent transcription.
Harrop
J A
JA
Department of Molecular and Cellular Immunology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
McDonnell
P C
PC
Brigham-Burke
M
M
Lyn
S D
SD
Minton
J
J
Tan
K B
KB
Dede
K
K
Spampanato
J
J
Silverman
C
C
Hensley
P
P
DiPrinzio
R
R
Emery
J G
JG
Deen
K
K
Eichman
C
C
Chabot-Fletcher
M
M
Truneh
A
A
Young
P R
PR
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000187:drug effects; D014018:Tissue Distribution; D018808:Transcription Factor AP-1 / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D006131:Growth Inhibitors; D006133:Growth Substances; D008024:Ligands; D008565:Membrane Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; D018808:Transcription Factor AP-1; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha