Costimulatory signal provided by a B-lymphoblastoid cell line and its Ia-negative variant.

Reiser, Hans; Benacerraf, Baruj

doi:10.1073/pnas.86.24.10069

Cited by 17 publications

(16 citation statements)

References 47 publications

(18 reference statements)

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“…The role of the APC in providing the second signal has been established through the use of lectins such as Con A and through the use of anti-TCR antibodies. Purified T cells respond to these stimuli only in the presence of certain MHC class II' and MHC class II-accessory cells (24,39). Thus a second signal, distinct from the MHC proteins, is required for T-cell activation.…”

Section: Discussionmentioning

confidence: 99%

“…Chinese hamster ovary (CHO), CHO-mB7, and CHOmB7.S8 cells were fixed for 15 min at room temperature with 1% paraformaldehyde in phosphate-buffered saline. Microcultures were set up in duplicates in 96-well plates as previously described (24,25,27). Lymphokine content was assayed on the HT-2 indicator cell line.…”

Section: Introductionmentioning

confidence: 99%

“…The following mAbs were used in this study: Cell Cultures. T cells were purified as previously described (24,25). Briefly, splenocytes were depleted of erythrocytes by treatment with Tris/NH4C1.…”

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confidence: 99%

“…T cells were enriched by nylon wool fractionation (26). CD4+ T cells from BALB/c or AKR mice were purified by treatment with a mixture of anti-MHC class II and anti-CD8 mAbs and rabbit complement (Cedarlane Laboratories, Hornby, ON, Canada) (24,25). Chinese hamster ovary (CHO), CHO-mB7, and CHOmB7.S8 cells were fixed for 15 min at room temperature with 1% paraformaldehyde in phosphate-buffered saline.…”

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Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.

Reiser

Freeman

Razi-Wolf

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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114

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We demonstrate that the murine B7 (mB7) protein is a potent costimulatory molecule for the activation of resting murine CD4+ T cells through the T-cell receptor (TCR)/CD3 complex. Stable mB7-transfected Chinese hamster ovary cells, but not vector-transfected controls, synergize with anti-CD3 monoclonal antibody and Con A-induced T-cell activation, resulting ultimately in proliferation. mB7 exerted its effect by inducing production of interleukin 2 and expression of the interleukin 2 receptor. Thus, mB7 costimulates T-cell activation through the TCR/CD3 complex by positively modulating the normal pathway of T-cell expansion. In contrast to the pronounced effect of mB7 on the activation of T cells through the TCR/CD3 complex, the mB7-transfected CHO cell line costimulated T-cell activation via the glycosylphosphatidylinositol-anchored proteins Thy-1 and Ly-6A.2 only inefficiently. Finally, the combination of a calcium ionophore and mB7 is not sufficient to cause T-cell proliferation, while the combination of a calcium ionophore and phorbol 12-myristate 13-acetate (PMA) stimulates T cells efficiently. The signals that mB7 and PMA provide for murine T lymphocyte activation are therefore not interchangeable, although both costimulate activation through the TCR/CD3 complex.Stimulation of highly purified CD4+ T lymphocytes with peptide-major histocompatibility complex (MHC) complexes, monoclonal antibodies (mAbs) against T-cell receptor (TCR)/CD3 complexes, lectins, or mAbs against the glycosyl-phosphatidylinositol (GPI)-anchored proteins Thy-1 and Ly-6A.2 does not lead to cell proliferation or lymphokine secretion. The above activation pathways require a second, costimulatory, signal for lymphokine gene expression and proliferation that is provided by an antigen-presenting cell (APC) or by pharmacological reagents such as phorbol 12-myristate 13-acetate (PMA) (1, 2).The nature of the costimulatory signal appears to be dependent upon the subset of CD4+ T cells that is activated. On the basis of their capacity to secrete specific lymphokines, two types of murine CD4+ T-helper cells were defined originally. Th-1 clones synthesize interleukin (IL)-2, interferon y, and lymphotoxin, whereas Th-2 clones secrete IL-4, IL-5, and IL-6 (3). In the case of Th-2 type CD4+ T cells, this costimulatory signal appears to be IL-1 (4). In contrast, the nature of the costimulatory signal for Th-1-type CD4+ T cells is unknown. Recent data in the human system suggest that B7, a 45-to 60-kDa cell surface glycoprotein present on activated B cells and on interferon-y-stimulated monocytes/macrophages (5, 6), may be costimulatory for Th-1 CD4+ T cells. Transfected cell lines that express human B7 or recombinant B7-immunoglobulin fusion protein can synergize with anti-CD3 or phytohemagglutinin-driven T-cell activation (7-9). Furthermore, binding of mAbs to CD28, a 44-kDa homodimeric T-cell glycoprotein that is a receptor for B7 (10), can augment the proliferation or lymphokine secretion of T cells stimulated with suboptimal doses of anti...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.

Reiser

Freeman

Razi-Wolf

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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114

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“…We have recently described a murine glycoprotein, provisionally termed sgp-60, which is expressed on virtually all lymphocytes of both T-and B-cell origin (3)(4)(5). Antibody inhibition studies suggest a functional role for sgp-60 in CD4+ T lymphocytes: addition of the anti-sgp-60 monoclonal antibody (mAb) 5-8A10 or of its Fab fragment significantly inhibits the activation of purified T cells by the lectin Con A or by a mitogenic anti-CD3 mAb (3,4).…”

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Identification, by protein sequencing and gene transfection, of sgp-60 as the murine homologue of CD48.

Cabrero

Freeman

Lane

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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We have recently described a murine lymphocyte protein, provisionally termed sgp-60, which is expressed on virtually all lymphocytes of both T-and B-cell origin. A hamster monoclonal antibody to sgp-60 can inhibit interleukin-2 (IL-2) production, IL-2-receptor expression, and T-cell proliferation, events normally observed after stimulation of T cells with an antibody to the T-cell receptor/CD3 complex or with the lectin concanavalin A. Our previous studies did not reveal the molecular nature of the sgp-60 antigen. Purification of sgp-60 and protein sequencing demonstrate that sgp-60 is identical to the CD48 antigen, a ligand for the CD2 antigen, which is also called Blast-i in humans, BCM1 in mice, and OX-45 in rats. The identity of sgp-60 and CD48 was independently confirmed in gene transfection experiments. The antisgp-60 monoclonal antibody was selectively reactive with COS-7 ceUs transfected with a BCM1 cDNA clone but not with Kb-transfected controls. The results of the present report, together with our previous functional studies, may have implications for the role of CD2 and CD48 in murine T-cell activation.Antigen-specific CD4+ T inducer cells are critically involved in the generation of delayed-type hypersensitivity, antibody, and cytotoxic responses. Normally, CD4+ T cells are in a resting state. Most immune responses therefore depend on the prior activation of CD4+ T lymphocytes, their rapid proliferative expansion, and the lymphokines which they secrete (1).The activation of CD4+ T cells depends critically on cognate interactions of the T cell with an antigen-presenting cell (APC). Physiologic activation is imparted by a heterodimeric T-cell receptor (TCR) with specificity for antigenic peptides complexed to major histocompatibility complex (MHC) proteins. The TCR is associated with a set of nonvariable proteins, collectively termed CD3 (T3) (2). Besides the polypeptides forming the TCR/CD3 complex, a number of molecules participate in the T-cell activation process. Some function as cell-cell interaction molecules and some as signal-transducing elements, and some can serve both functions (2).We have recently described a murine glycoprotein, provisionally termed sgp-60, which is expressed on virtually all lymphocytes of both T-and B-cell origin (3-5). Antibody inhibition studies suggest a functional role for sgp-60 in CD4+ T lymphocytes: addition of the anti-sgp-60 monoclonal antibody (mAb) 5-8A10 or of its Fab fragment significantly inhibits the activation of purified T cells by the lectin Con A or by a mitogenic anti-CD3 mAb (3, 4). Proliferation, interleukin 2 (IL-2) production, IL-2 receptor expression, and generation of second messengers are all affected by the anti-sgp-60 mAb (3,4,6). Only a few antibodies affect T-cell function. Our experiments therefore suggest a role for sgp-60 in T-cell activation.Our previous studies did not reveal the molecular identity of the sgp-60 antigen. In the present report, we close this gap. Partial amino acid sequence of the sgp-60 antigen and gene transfe...

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The sgp‐60 mlecule is linked to the plasma membrane via a glycosylphosphatidylinositol anchor

Cabrero

Reiser

1991

Eur J Immunol

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We have recently identified a novel murine glycoprotein termed sgp-60, which is expressed on the cell surface of T and B lymphocytes. Because of the profound modulatory effects of sgp-60 on activation through the T cell receptor/CD3 complex, we have examined the membrane attachment domain of the molecule. sgp-60 is not expressed on the surface of variants of a T-T hybridoma cell line that are defective in glycosylphosphatidylinositol (GPI) anchor biosynthesis. In wild-type but not in mutant cells, sgp-60 can be labeled with palmitic acid. Furthermore, the molecule can be removed from the cell surface of both T and B lymphocytes by enzymatic digestion with a phosphatidylinositol-specific phospholipase C. We conclude that the sgp-60 molecule is linked to the plasma membrane via a GPI anchor.

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Costimulatory signal provided by a B-lymphoblastoid cell line and its Ia-negative variant.

Cited by 17 publications

References 47 publications

Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.

Murine B7 antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.

Identification, by protein sequencing and gene transfection, of sgp-60 as the murine homologue of CD48.

The sgp‐60 mlecule is linked to the plasma membrane via a glycosylphosphatidylinositol anchor

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