Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1.

Sánchez‐Madrid, Francisco; Simon, Paul; Thompson, S.J.; Springer, Timothy A.

doi:10.1084/jem.158.2.586

Cited by 238 publications

(104 citation statements)

References 42 publications

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“…To support the hypothesis that M17/4 anti-LFA-1 prevented arthritis by blocking LFA-1-mediated adhesion, rather than by another mechanism such as cross-linking LFA-1 and thereby altering leukocyte function, we tested mAb M18/2 (20). This mAb binds the CD18 subunit of ␤ 2 integrins, but does not interfere with LFA-1 binding to ICAM-1 or block T cell cytotoxicity.…”

Section: Anti-lfa-1 I-domain Mab Blocks the Development And Perpetuatmentioning

confidence: 99%

Manifestations of Inflammatory Arthritis Are Critically Dependent on LFA-1

Watts

Beurskens

Martín‐Padura

et al. 2005

The Journal of Immunology

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Leukocyte infiltration of synovial fluid and tissues is the hallmark of inflammatory arthritis. Selectins and β2 integrins have been implicated in the multistep process of leukocyte adhesion to vascular endothelium. However, previous work has revealed disparate requirements for leukocyte recruitments to specific anatomic locales. Moreover, the mechanisms regulating recruitment of leukocytes to the joint in inflammatory arthritis models are not fully understood. We hypothesized that β2 integrins, expressed on leukocytes, might play a pathogenic role in synovial inflammation. Using mice deficient in all β2 integrins (CD18 null mice), we demonstrate that expression of these heterodimeric adhesion molecules is critical for arthritis induction in the K/B × N serum transfer model. Using null-allele mice and blocking mAbs, we demonstrate specifically that CD11a/CD18 (LFA-1) is absolutely required for the development of arthritis in this model. Blocking mAbs further revealed an ongoing requirement for LFA-1 I-domain adhesive function in disease perpetuation. These findings suggest that the LFA-1 I-domain forms an attractive target for treatment of human inflammatory arthritis.

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Section: Anti-lfa-1 I-domain Mab Blocks the Development And Perpetuatmentioning

confidence: 99%

Manifestations of Inflammatory Arthritis Are Critically Dependent on LFA-1

Watts

Beurskens

Martín‐Padura

et al. 2005

The Journal of Immunology

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“…Rabbit antiserum to human GpIIIa (anti-a3 chain) was a gift from Dr. R. McKever (Oklahoma University, Norman, OK) and has previously been shown to react with mouse /33 integrin chains (7). Clone M18/2.a .8, secreting rat IgG reactive with mouse 02 integrin chains (8), was purchased from the American Type Culture Collection (Rockville, MD). Rat mAb to mouse LFA-1 (from clone M17/5.2) was purchased from Boehringer Mannheim Biochemicals (Indianapolis, IN).…”

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confidence: 99%

The mouse vitronectin receptor is a T cell activation antigen.

Moulder

Roberts

Shevach

et al. 1991

The Journal of Experimental Medicine

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ntegrins comprise a complex family of cell adhesion molecules involved in cell-cell and cell-extracellular matrix protein (ECMP)t interactions (1). At least three subfamilies have been defined on the basis of the association ofany of a number of at chains with a common /3 chain (2) . We have previously characterized two mAbs (H9.2B8 and 8.1802) that identified a novel integrin expressed on murine y/S and a//3 T cell lines and hybridomas as well as on T cells activated for prolonged periods of time (7-21 d) by mitogens or alloantigens. This integrin mediated adhesion to fibronectin, vitronectin, and fibrinogen, and the two mAbs in combination, as well as the tetrapeptide RGDS alone, could inhibit the binding of cell lines to these ECMP (3) . In the present report, we make use of a number of antisera to the vitronectin receptor (VNR) and demonstrate that this novel integrin is the murine homologue of the human VNR, thereby demonstrating for the first time that the VNR is present on mouse T lymphocytes and that the expression of this (33 integrin can be upregulated by activation. SummaryIn this report, we demonstrate that the T cell activation antigen, recognized by monoclonal antibody HUN, is the murine homologue of the vitronectin receptor (VNR) and, thereby, we provide initial evidence that VNR is expressed on lymphoid cells . VNR is expressed on a variety of T cell lines, tumors, and Con A-activated splenocytes, but not resting T cells, and is capable of binding to the extracellular matrix proteins fibronectin, fibrinogen, and vitronectin, via the tripeptide sequence RGD. There was no evidence of novel a chains pairing with the VNR ct chain, as has been demonstrated in some human cells . In view of recent studies demonstrating that this molecule functions as an accessory molecule in T cell activation, the VNR may play an important role in mouse T cell functions.Cell Lines. Dendritic epidermal T cell (DETC) line T195 and its corresponding hybridoma (T195/BW) derived from fusion to BW5147 have been previously described (4-6).Antibodies. mAb H9 .2B8 is a hamster mAb obtained after immunizations with mouse DETC lines (3). Rabbit anti-human VNR

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“…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; American Type Culture Collection, Rockville, MD), 11 and hamster anti-mouse CD3 mAb (145-2C11; a kind gift of Dr J Bluestone, University of Calfornia, San Francisco). 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.…”

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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Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1.

Cited by 238 publications

References 42 publications

Manifestations of Inflammatory Arthritis Are Critically Dependent on LFA-1

Manifestations of Inflammatory Arthritis Are Critically Dependent on LFA-1

The mouse vitronectin receptor is a T cell activation antigen.

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

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