B7 Antigen

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H Reiser - One of the best experts on this subject based on the ideXlab platform.

  • The Costimulatory Molecule B7 Is Expressed in the Medullary Region of the Murine Thymus
    Immunology, 1994
    Co-Authors: H Reiser, E E Schneeberger
    Abstract:

    Several laboratories, including our own, have previously shown that the B7 Antigen, a glycoprotein expressed on activated B cells, macrophages and dendritic cells, can provide a potent costimulatory signal for peripheral murine T lymphocytes. In the present report we have analysed the expression and function of B7 in the murine thymus. The expression of B7 was demonstrated histochemically. B7-expressing cells were present in the thymic medulla but virtually absent from the cortex. Further analysis by immunofluorescence and flow fluorocytometry revealed that the B7-positive cells also expressed major histocompatibility complex (MHC) class II molecules. Both epithelial and dendritic cells expressed the B7 Antigen. Finally, although we have demonstrated expression of mB7 in the murine thymus, we have been unable to detect a function for this Antigen in this organ. The implications of these findings are discussed.

  • Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor.
    Proceedings of the National Academy of Sciences of the United States of America, 1993
    Co-Authors: Ziba Razi-wolf, Frances Galvin, Gary S. Gray, H Reiser
    Abstract:

    Abstract Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complex complexes and costimulatory signals provided by Antigen-presenting cells (APCs). The best-characterized costimulatory molecule to date is the B7 Antigen, a member of the immunoglobulin family that binds two receptors, CD28 and CTLA-4, expressed on the T-cell surface. Using the anti-mouse B7 (mB7) monoclonal antibody (mAb) 16-10A1, which we recently developed, we found that mB7 is indeed an important costimulatory ligand for the Antigen-specific activation of murine T cells by B lymphocytes. Three lines of evidence suggest, however, the existence of at least one additional ligand for the CTLA-4 receptor. First, a soluble fusion protein of human CTLA-4 and the IgG1 Fc region, termed CTLA4Ig, blocks better than the anti-mB7 mAb the allogeneic stimulation of T cells by unfractionated splenic APCs. Second, saturating amounts of anti-mB7 mAb do not significantly block binding of fluorescein isothiocyanate-conjugated CTLA4Ig to activated splenic APCs. Furthermore, CTLA4Ig but not the anti-mB7 mAb reacts with the M12 and M12.C3 cell lines. The identification of an additional ligand for CTLA-4 may have applications to the treatment of autoimmune disease and transplant-associated disorders.

  • Effects of cyclosporin A, FK 506, and mycalamide A on the activation of murine CD4+ T cells by the murine B7 Antigen.
    European journal of immunology, 1993
    Co-Authors: Frances Galvin, Lee M. Nadler, Gordon J. Freeman, Baruj Benacerraf, Ziba Razi-wolf, H Reiser
    Abstract:

    The murine B7 (mB7) protein is a potent co-stimulatory molecule for the activation of murine CD4+ T cells. We have previously shown that stable mB7-transfected Chinese hamster ovary (CHO) cells synergize with either anti-CD3 monoclonal antibodies (mAb) or concanavalin A to stimulate T cell activation. In addition, mB7 can synergize with phorbol 12-myristate 13-acetate (PMA) to induce T cell activation in an alternative pathway. In the present report we describe the effects of three immunosuppressive drugs, cyclosporin A (CsA), FK 506, and mycalamide A on mB7-mediated T cell activation. The immuno-philin ligands CsA and FK 506 block activation of murine CD4+ T cells by the combination of anti-CD3 mAb and CHO-mB7 cells but do not affect activation by CHO-mB7 cells and PMA. These results support the relevance of pharmacological studies of immunosuppressive compounds in the murine model prior to their application in man. In contrast to the effects of CsA and FK 506, mycalamide A blocks activation of murine CD4+ T cells by anti-CD3 mAb and mB7 as well as activation by mB7 and PMA. On a molar basis, mycalamide A appears to be at least 10-fold more potent than FK 506 which is 100-fold more potent than CsA. Because of its effects on multiple activation pathways and because of its potency, mycalamide A could have considerable therapeutic potential.

  • Murine B7 Antigen provides a sufficient costimulatory signal for Antigen-specific and MHC-restricted T cell activation.
    Journal of immunology (Baltimore Md. : 1950), 1992
    Co-Authors: Frances Galvin, Lee M. Nadler, Gordon J. Freeman, Baruj Benacerraf, Ziba Razi-wolf, William P. Hall, H Reiser
    Abstract:

    We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation.

  • expression and function of the murine B7 Antigen the major costimulatory molecule expressed by peritoneal exudate cells
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: Ziba Raziwolf, Lee M. Nadler, Gordon J. Freeman, Frances Galvin, Baruj Benacerraf, H Reiser
    Abstract:

    Abstract The murine B7 (mB7) protein is a potent costimulatory molecule for the T-cell receptor (TCR)-mediated activation of murine CD4+ T cells. We have previously shown that stable mB7-transfected Chinese hamster ovary (CHO) cells but not vector-transfected controls synergize with either anti-CD3 monoclonal antibody-induced or concanavalin A-induced T-cell activation, resulting ultimately in lymphokine production and proliferation. We now have generated a hamster anti-mB7 monoclonal antibody. This reagent recognizes a protein with an apparent molecular mass of 50-60 kDa. The mB7 Antigen is expressed on activated B cells and on peritoneal exudate cells (PECs). Antibody blocking experiments demonstrate that mB7 is the major costimulatory molecule expressed by PECs for the activation of murine CD4+ T cells. This suggests an important role for mB7 during immune-cell interactions. We have also surveyed a panel of murine cell lines capable of providing costimulatory activity. Our results indicate that mB7 is the major costimulatory molecule on some but not all cell lines and that there may be additional molecules besides mB7 that can costimulate the activation of murine CD4+ T cells.

G Cavanagh - One of the best experts on this subject based on the ideXlab platform.

  • Identification of an HLA-B7 serological variant and its characterization by sequencing based typing.
    Tissue antigens, 2000
    Co-Authors: P P Dunn, V Carter, A Dunn, S Day, S V Fuggle, J Ross, G Cavanagh
    Abstract:

    We have identified an HLA-B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence-specific primers (PCR-SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti-HLA antisera, gave disparate results for the B Antigens. Monoclonal antibodies identified B7 and B8 Antigens but polyclonal antisera recognised only the B8 Antigen. PCR using sequencing based typing (PCR-SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA-B*07 allele was isolated by allele-specific PCR and was shown to have a mutation, G-->T, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 Antigen-specific epitope recognised by tissue typing polyclonal antisera.

  • Identification of an HLA‐B7 serological variant and its characterization by sequencing based typing
    Tissue Antigens, 1999
    Co-Authors: P P Dunn, V Carter, A Dunn, S Day, S V Fuggle, J Ross, G Cavanagh
    Abstract:

    : We have identified an HLA-B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence-specific primers (PCR-SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti-HLA antisera, gave disparate results for the B Antigens. Monoclonal antibodies identified B7 and B8 Antigens but polyclonal antisera recognised only the B8 Antigen. PCR using sequencing based typing (PCR-SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA-B*07 allele was isolated by allele-specific PCR and was shown to have a mutation, GT, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 Antigen-specific epitope recognised by tissue typing polyclonal antisera ( Note).

Lee M. Nadler - One of the best experts on this subject based on the ideXlab platform.

  • Effects of cyclosporin A, FK 506, and mycalamide A on the activation of murine CD4+ T cells by the murine B7 Antigen.
    European journal of immunology, 1993
    Co-Authors: Frances Galvin, Lee M. Nadler, Gordon J. Freeman, Baruj Benacerraf, Ziba Razi-wolf, H Reiser
    Abstract:

    The murine B7 (mB7) protein is a potent co-stimulatory molecule for the activation of murine CD4+ T cells. We have previously shown that stable mB7-transfected Chinese hamster ovary (CHO) cells synergize with either anti-CD3 monoclonal antibodies (mAb) or concanavalin A to stimulate T cell activation. In addition, mB7 can synergize with phorbol 12-myristate 13-acetate (PMA) to induce T cell activation in an alternative pathway. In the present report we describe the effects of three immunosuppressive drugs, cyclosporin A (CsA), FK 506, and mycalamide A on mB7-mediated T cell activation. The immuno-philin ligands CsA and FK 506 block activation of murine CD4+ T cells by the combination of anti-CD3 mAb and CHO-mB7 cells but do not affect activation by CHO-mB7 cells and PMA. These results support the relevance of pharmacological studies of immunosuppressive compounds in the murine model prior to their application in man. In contrast to the effects of CsA and FK 506, mycalamide A blocks activation of murine CD4+ T cells by anti-CD3 mAb and mB7 as well as activation by mB7 and PMA. On a molar basis, mycalamide A appears to be at least 10-fold more potent than FK 506 which is 100-fold more potent than CsA. Because of its effects on multiple activation pathways and because of its potency, mycalamide A could have considerable therapeutic potential.

  • Murine B7 Antigen provides a sufficient costimulatory signal for Antigen-specific and MHC-restricted T cell activation.
    Journal of immunology (Baltimore Md. : 1950), 1992
    Co-Authors: Frances Galvin, Lee M. Nadler, Gordon J. Freeman, Baruj Benacerraf, Ziba Razi-wolf, William P. Hall, H Reiser
    Abstract:

    We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation.

  • expression and function of the murine B7 Antigen the major costimulatory molecule expressed by peritoneal exudate cells
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: Ziba Raziwolf, Lee M. Nadler, Gordon J. Freeman, Frances Galvin, Baruj Benacerraf, H Reiser
    Abstract:

    Abstract The murine B7 (mB7) protein is a potent costimulatory molecule for the T-cell receptor (TCR)-mediated activation of murine CD4+ T cells. We have previously shown that stable mB7-transfected Chinese hamster ovary (CHO) cells but not vector-transfected controls synergize with either anti-CD3 monoclonal antibody-induced or concanavalin A-induced T-cell activation, resulting ultimately in lymphokine production and proliferation. We now have generated a hamster anti-mB7 monoclonal antibody. This reagent recognizes a protein with an apparent molecular mass of 50-60 kDa. The mB7 Antigen is expressed on activated B cells and on peritoneal exudate cells (PECs). Antibody blocking experiments demonstrate that mB7 is the major costimulatory molecule expressed by PECs for the activation of murine CD4+ T cells. This suggests an important role for mB7 during immune-cell interactions. We have also surveyed a panel of murine cell lines capable of providing costimulatory activity. Our results indicate that mB7 is the major costimulatory molecule on some but not all cell lines and that there may be additional molecules besides mB7 that can costimulate the activation of murine CD4+ T cells.

  • The gene for B7, a costimulatory signal for T-cell activation, maps to chromosomal region 3q13.3-3q21.
    Blood, 1992
    Co-Authors: Gordon J. Freeman, Arnold S. Freedman, C.m. Disteche, John G. Gribben, David Adler, James Dougery, Lee M. Nadler
    Abstract:

    B7 is an activation Antigen expressed on activated B cells and gamma- interferon-stimulated monocytes. The B7 Antigen is the natural ligand for CD28 on T cells. After engagement of T-cell receptor with Antigen in association with major histocompatibility complex class II, a second signal mediated through the binding of B7 to CD28 greatly upregulates the production of multiple lymphokines. We have now mapped the B7 gene to human chromosome 3 using the technique of polymerase chain reaction on a panel of hamster x human somatic cell hybrid DNAs. We have further localized the gene to 3q13.3–3q21 using in situ hybridization on human metaphase chromosomes. Trisomy of chromosome 3 is a recurrent chromosome change seen in various lymphomas and lymphoproliferative diseases, particularly diffuse, mixed, small, and large cell lymphomas, human T-cell lymphotropic virus type I-induced adult T-cell leukemia, and angioimmunoblastic lymphadenopathy. A number of chromosomal defects involving 3q21 have been described in acute myeloid leukemia and also in myelodysplastic and myeloproliferative syndromes. The mapping of B7 may permit further insight into disease states associated with aberrant lymphocyte activation and lymphokine synthesis.

  • Murine B7 Antigen provides an efficient costimulatory signal for activation of murine T lymphocytes via the T-cell receptor/CD3 complex.
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: H Reiser, Gordon J. Freeman, Baruj Benacerraf, Ziba Razi-wolf, Claude D. Gimmi, Lee M. Nadler
    Abstract:

    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.

P P Dunn - One of the best experts on this subject based on the ideXlab platform.

  • Identification of an HLA-B7 serological variant and its characterization by sequencing based typing.
    Tissue antigens, 2000
    Co-Authors: P P Dunn, V Carter, A Dunn, S Day, S V Fuggle, J Ross, G Cavanagh
    Abstract:

    We have identified an HLA-B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence-specific primers (PCR-SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti-HLA antisera, gave disparate results for the B Antigens. Monoclonal antibodies identified B7 and B8 Antigens but polyclonal antisera recognised only the B8 Antigen. PCR using sequencing based typing (PCR-SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA-B*07 allele was isolated by allele-specific PCR and was shown to have a mutation, G-->T, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 Antigen-specific epitope recognised by tissue typing polyclonal antisera.

  • Identification of an HLA‐B7 serological variant and its characterization by sequencing based typing
    Tissue Antigens, 1999
    Co-Authors: P P Dunn, V Carter, A Dunn, S Day, S V Fuggle, J Ross, G Cavanagh
    Abstract:

    : We have identified an HLA-B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence-specific primers (PCR-SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti-HLA antisera, gave disparate results for the B Antigens. Monoclonal antibodies identified B7 and B8 Antigens but polyclonal antisera recognised only the B8 Antigen. PCR using sequencing based typing (PCR-SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA-B*07 allele was isolated by allele-specific PCR and was shown to have a mutation, GT, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 Antigen-specific epitope recognised by tissue typing polyclonal antisera ( Note).

Frances Galvin - One of the best experts on this subject based on the ideXlab platform.

  • Evidence for an additional ligand, distinct from B7, for the CTLA-4 receptor.
    Proceedings of the National Academy of Sciences of the United States of America, 1993
    Co-Authors: Ziba Razi-wolf, Frances Galvin, Gary S. Gray, H Reiser
    Abstract:

    Abstract Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complex complexes and costimulatory signals provided by Antigen-presenting cells (APCs). The best-characterized costimulatory molecule to date is the B7 Antigen, a member of the immunoglobulin family that binds two receptors, CD28 and CTLA-4, expressed on the T-cell surface. Using the anti-mouse B7 (mB7) monoclonal antibody (mAb) 16-10A1, which we recently developed, we found that mB7 is indeed an important costimulatory ligand for the Antigen-specific activation of murine T cells by B lymphocytes. Three lines of evidence suggest, however, the existence of at least one additional ligand for the CTLA-4 receptor. First, a soluble fusion protein of human CTLA-4 and the IgG1 Fc region, termed CTLA4Ig, blocks better than the anti-mB7 mAb the allogeneic stimulation of T cells by unfractionated splenic APCs. Second, saturating amounts of anti-mB7 mAb do not significantly block binding of fluorescein isothiocyanate-conjugated CTLA4Ig to activated splenic APCs. Furthermore, CTLA4Ig but not the anti-mB7 mAb reacts with the M12 and M12.C3 cell lines. The identification of an additional ligand for CTLA-4 may have applications to the treatment of autoimmune disease and transplant-associated disorders.

  • Effects of cyclosporin A, FK 506, and mycalamide A on the activation of murine CD4+ T cells by the murine B7 Antigen.
    European journal of immunology, 1993
    Co-Authors: Frances Galvin, Lee M. Nadler, Gordon J. Freeman, Baruj Benacerraf, Ziba Razi-wolf, H Reiser
    Abstract:

    The murine B7 (mB7) protein is a potent co-stimulatory molecule for the activation of murine CD4+ T cells. We have previously shown that stable mB7-transfected Chinese hamster ovary (CHO) cells synergize with either anti-CD3 monoclonal antibodies (mAb) or concanavalin A to stimulate T cell activation. In addition, mB7 can synergize with phorbol 12-myristate 13-acetate (PMA) to induce T cell activation in an alternative pathway. In the present report we describe the effects of three immunosuppressive drugs, cyclosporin A (CsA), FK 506, and mycalamide A on mB7-mediated T cell activation. The immuno-philin ligands CsA and FK 506 block activation of murine CD4+ T cells by the combination of anti-CD3 mAb and CHO-mB7 cells but do not affect activation by CHO-mB7 cells and PMA. These results support the relevance of pharmacological studies of immunosuppressive compounds in the murine model prior to their application in man. In contrast to the effects of CsA and FK 506, mycalamide A blocks activation of murine CD4+ T cells by anti-CD3 mAb and mB7 as well as activation by mB7 and PMA. On a molar basis, mycalamide A appears to be at least 10-fold more potent than FK 506 which is 100-fold more potent than CsA. Because of its effects on multiple activation pathways and because of its potency, mycalamide A could have considerable therapeutic potential.

  • Murine B7 Antigen provides a sufficient costimulatory signal for Antigen-specific and MHC-restricted T cell activation.
    Journal of immunology (Baltimore Md. : 1950), 1992
    Co-Authors: Frances Galvin, Lee M. Nadler, Gordon J. Freeman, Baruj Benacerraf, Ziba Razi-wolf, William P. Hall, H Reiser
    Abstract:

    We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation.

  • expression and function of the murine B7 Antigen the major costimulatory molecule expressed by peritoneal exudate cells
    Proceedings of the National Academy of Sciences of the United States of America, 1992
    Co-Authors: Ziba Raziwolf, Lee M. Nadler, Gordon J. Freeman, Frances Galvin, Baruj Benacerraf, H Reiser
    Abstract:

    Abstract The murine B7 (mB7) protein is a potent costimulatory molecule for the T-cell receptor (TCR)-mediated activation of murine CD4+ T cells. We have previously shown that stable mB7-transfected Chinese hamster ovary (CHO) cells but not vector-transfected controls synergize with either anti-CD3 monoclonal antibody-induced or concanavalin A-induced T-cell activation, resulting ultimately in lymphokine production and proliferation. We now have generated a hamster anti-mB7 monoclonal antibody. This reagent recognizes a protein with an apparent molecular mass of 50-60 kDa. The mB7 Antigen is expressed on activated B cells and on peritoneal exudate cells (PECs). Antibody blocking experiments demonstrate that mB7 is the major costimulatory molecule expressed by PECs for the activation of murine CD4+ T cells. This suggests an important role for mB7 during immune-cell interactions. We have also surveyed a panel of murine cell lines capable of providing costimulatory activity. Our results indicate that mB7 is the major costimulatory molecule on some but not all cell lines and that there may be additional molecules besides mB7 that can costimulate the activation of murine CD4+ T cells.