Identification of an Alternatively Spliced Form of the Murine Homolog of B7

Inobe, Manabu; Linsley, Peter S.; Ledbetter, Jeffrey A.; Nagai, Y.; Tamakoshi, Masatada; Uede, T

doi:10.1006/bbrc.1994.1469

Cited by 41 publications

(32 citation statements)

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“…33,34 On the other hand, a splice variant has been identified in mice which lacks the C-like domain but still is capable of binding to CD28Ig, suggesting that the C-like domain is not essential for CD28-binding. 35 CD86 A304T introduces a potential phosphorylation site in the cytoplasmic region; however, no information is available whether this substitution may influence the signal transduction pathway. Therefore, it is not clear at present whether the amino acid substitutions of CD80 and CD86 detected in this study have a substantial effect on the function of these molecules.…”

Section: Discussionmentioning

confidence: 99%

New polymorphisms of human CD80 and CD86: lack of association with rheumatoid arthritis and systemic lupus erythematosus

et al. 2000

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Section: Discussionmentioning

confidence: 99%

New polymorphisms of human CD80 and CD86: lack of association with rheumatoid arthritis and systemic lupus erythematosus

et al. 2000

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“…For example, multiple murine B7-2 alternatively spliced products have been identified (13). Additionally, an alternatively spliced form of murine B7-1 lacking the Ig C region-like extracellular domain has been described (14). Resolution of the B7-1 genomic organization in mouse and human indicates that both the transmembrane and cytoplasmic domains are encoded by separate exons, making it possible to exclude these regions without disrupting the extracellular domains (15,16).…”

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confidence: 99%

Primary Structure and Functional Characterization of a Soluble, Alternatively Spliced Form of B7-1

Faas

Giannoni

Mickle

et al. 2000

The Journal of Immunology

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Recent studies have suggested that soluble forms of B7-1 and B7-2 may exist, but transcripts that code for these molecules have not been previously described. In this study, we report the cloning and characterization of an alternatively spliced soluble form of porcine B7-1 (sB7-1) that lacks exons coding for both the transmembrane and cytoplasmic domains. Northern blot analysis of RNA from alveolar macrophages revealed an approximate 3:1 ratio of the transmembrane form of B7-1 mRNA relative to sB7-1 mRNA. Porcine B7-1 was present on the surface of both B and T cells following stimulation with PMA/ionomycin. A histidine-tagged form of porcine sB7-1 (sB7-1-His) interacted with both CD28 and CTLA-4, and effectively blocked IL-2 production from human responder cells stimulated with PHA and either porcine or human stimulator cells. In addition, sB7–1-His inhibited human T cell proliferation in response to porcine or human peripheral blood leukocytes. This study is the first report of an alternatively spliced form of B7 that codes for a soluble protein. Furthermore, these data demonstrate that porcine B7-1 interacts with the human receptors CD28 and CTLA-4, suggesting a potential role for this molecule in pig to human xenotransplantation. Possible physiological functions for the soluble form of B7-1 are discussed.

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“…Besides these extrinsic manipulations of B7-mediated immunity, our previous studies 3,13 showed that lack of the IgC-like domain of B7-1 resulting from an alternative splicing of mRNA decreases affinity to CTLA- Since osteosarcoma cell lines are not easily established from individual patients, in vivo transfection of B7-1 gene rather than ex vivo transfection is more suitable for clinical situations. Our previous 2 as well as the present study consistently supported the usefulness of adenovirus vector for transferring B7-1 genes into osteosarcomas.…”

Section: Discussionmentioning

confidence: 99%

“…12 Fusion proteins, CTLA-4Ig and CD28Ig, which consist of an extracellular portion of mouse cytolytic T-lymphocyte-associated antigen-4 (CTLA-4) or CD28 and Fc portion of human immunoglobulin G1, respectively, were prepared as described previously. 13 Construction of B7-1 and B7-1/Fas chimeric cDNAs…”

Section: Animals Cell Lines and Reagentsmentioning

confidence: 99%

Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer

et al. 2003

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To establish an effective B7-based gene therapy against osteosarcoma, we transferred B7-1/Fas chimeric gene adenovirally into poorly immunogenic osteosarcoma cells. We found that adenovirus-mediated rat B7-1/Fas gene transfer induced (i) expression of rat B7-1/Fas chimeric molecules in osteosarcoma cells, (ii) activation of murine T cells, (iii) apoptosis of murine osteosarcoma cells in the presence of anti-rat B7-1 mAb in vitro, and (iv) therapeutic effects more prominently than B7-1 gene transfer on the development of pulmonary metastasis and survival of mice. These findings collectively support the therapeutic value of adenovirusmediated B7-1/Fas gene transfer on poorly immunogenic osteosarcoma, which is resistant to a treatment protocol using transduction of B7-1 alone. Cancer Gene Therapy (2003) 10, 717-725. doi:10.1038/sj.cgt.7700624Keywords: B7-1; Fas; chimeric gene; adenovirus; osteosarcoma; apoptosis T reatment of patients with osteosarcoma, especially those resistant to current chemotherapy protocols, has been a major challenge. Active immunotherapy is a potential clue for overcoming such therapeutic difficulties. Using a rat syngeneic model system, we demonstrated that B7-1-transfected tumor vaccine as well as adenovirus-mediated in vivo B7-1 gene transfer induces antitumor immunity against pre-established pulmonary metastasis of osteosarcoma. 1,2 On the other hand, we also found that B7-1-transfected vaccine has limited efficacy on a poorly immunogenic osteosarcoma cell line. 3 As seen in other studies, 4,5 the effect of B7-1 costimulation on T-cell-mediated tumor immunity varies depending on the inherent immunogenecity of tumors. To obtain more potent antitumor effects of B7-expressing osteosarcoma vaccine, we constructed a chimeric gene consisting of the extracellular domain of B7-1 and the transmembrane and intracellular domains of Fas, a member of the tumor necrosis factor family acting as an inducer of apoptosis. Materials and methods Animals, cell lines and reagentsMale C3H/He and BALB/c mice and LEW rats, 6-week old, were purchased from Japan SLC Inc. (Hamamatsu, Japan), and housed in a specific pathogen-free animal facility in our Institute.A murine osteosarcoma cell line, LM8, derived from Dunn osteosarcoma was kindly provided by the Department of Orthopaedics, Osaka University Graduate School of Medicine. 6 Chinese hamster ovary (CHO) cells expressing murine B7-1 (mB7-1-CHO) were prepared as described previously. 7 LM8 cells were maintained in DMEM (GIBCO, Grand Island, NY) containing 10% fetal calf serum (GIBCO), vitamin solution, sodium pyruvate, nonessential amino acids and l-glutamate at 371C in 5% CO 2 , and mB7-1-CHO cells in aMEM (GIBCO) containing 10% fetal calf serum.Monoclonal antibodies (mAbs) used were mouse antirat B7-1 mAb (3H5), 8 rat anti-mouse B7-1 mAb (1G10; PharMingen, San Diego, CA), 9 rat anti-mouse MHCclass I (H-2D k ) mAb (15-5-5; PharMingen), rat antimouse MHC-class II mAb (1E4; a kind gift from Dr K Ogasawara, Hokkaido University), 10 rat anti-mouse Mac-1 mAb (M1/70...

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Identification of an Alternatively Spliced Form of the Murine Homolog of B7

Cited by 41 publications

References 0 publications

New polymorphisms of human CD80 and CD86: lack of association with rheumatoid arthritis and systemic lupus erythematosus

New polymorphisms of human CD80 and CD86: lack of association with rheumatoid arthritis and systemic lupus erythematosus

Primary Structure and Functional Characterization of a Soluble, Alternatively Spliced Form of B7-1

Concurrent induction of T-cell activation and apoptosis of osteosarcoma cells by adenovirus-mediated B7-1/Fas chimeric gene transfer

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