Molecular and biological characterization of human 4-1BB and its ligand
| Autor: | Raymond G. Goodwin, Elizabeth A. Baker, Craig A. Smith, Terri Davis-Smith, Wenie S. Din, Ben A. Falk, Grant R. Sutherland, Mark R. Alderson, Teresa W. Tough, Richard J. Armitage, Eileen R. Roux |
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| Rok vydání: | 1994 |
| Předmět: |
Male
DNA Complementary medicine.drug_class T cell Immunology Molecular Sequence Data Clone (cell biology) Receptors Nerve Growth Factor Biology Monoclonal antibody Lymphocyte Activation Transfection Binding Competitive Receptors Tumor Necrosis Factor chemistry.chemical_compound Mice Tumor Necrosis Factor Receptor Superfamily Member 9 Antigens CD Complementary DNA medicine Immunology and Allergy Animals Humans Amino Acid Sequence RNA Messenger Cells Cultured Genomic Library Mice Inbred BALB C Membrane Glycoproteins Base Sequence Cell Death T-cell receptor Antibodies Monoclonal Chromosome Mapping Flow Cytometry Molecular biology Fusion protein 4-1BB ligand medicine.anatomical_structure chemistry Expression cloning |
| Zdroj: | European journal of immunology. 24(9) |
| ISSN: | 0014-2980 |
| Popis: | 4-1BB was originally described as a cDNA expressed by activated murine T cells and subsequently demonstrated to encode a member of the tumor necrosis factor receptor family of integral membrane proteins. Recently, we identified and cloned a murine ligand for 4-1BB (mu4-1BB-L) and demonstrated it to be a member of an emerging family of ligands with structural homology to tumor necrosis factor. To characterize further the role of 4-1BB in the immune response we undertook to clone the human homologue of 4-1BB-L. However, attempts to isolate a cDNA encoding the human 4-1BB-L by cross-hybridization with the murine cDNA were unsuccessful. Therefore we first utilized cross-species hybridization to isolate a cDNA encoding human 4-1BB (hu4-1BB). A fusion protein consisting of the extracellular portion of hu4-1BB coupled to the Fc region of human immunoglobulin G1 (hu4-1BB.Fc) was then used to identify and clone a gene for human 4-1BB-L from an activated CD4+ T cell clone using a direct expression cloning strategy. Human 4-1BB-L shows 36% amino acid identity with its murine counterpart and maps to chromosome 19p13.3. Scatchard analysis demonstrated high-affinity binding of hu4-1BB.Fc to either native or recombinant human 4-1BB-L. Both monoclonal antibody to hu4-1BB and cells transfected with hu4-1BB-L induced a strong proliferative response in mitogen co-stimulated primary T cells. In contrast, ligation of 4-1BB on T cell clones enhanced activation-induced cell death when triggered by engagement of the TCR/CD3 complex. |
| Databáze: | OpenAIRE |
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