Abstract:
:This study describes a general strategy to produce hybrid monoclonal antibodies that are capable of targeting human cytotoxic T lymphocytes (CTL) against any cell carrying the appropriate target antigen. This is done by fusing a HAT-sensitive, G418-resistant anti-T3 hybridoma with immune spleen cells (or with other hybridomas) that produce antibodies against the desired target antigen. In the hybrid hybridomas the reassortment of Ig heavy and light chains results in the production of bifunctional antibody molecules. Because of their double specificity, these antibodies are able to bridge human CTL to target cells and trigger cytotoxic function. We have isolated several stable hybrid hybridomas in which one specificity is against T3 and one either against HLA antigens (class II, DC-1, A3), human Ig (IgM, IgE, kappa), Toxoplasma gondii or an ovary carcinoma-associated antigen. In all of these cases we show that culture supernatants can efficiently and specifically target any CTL clone against any target cell that possesses the relevant surface antigen recognized by the antibody. Furthermore, the killing requires as little as 0.1 ng/ml of antibody, occurs at effector to target ratios comparable to those used in conventional cytotoxic assays and does not affect bystander cells. Nonspecific killing of Fc receptor-positive cells can be avoided using F(ab')2 fragments. As an example, we show that it is possible to change the major histocompatibility complex class and allospecificity of a CTL clone and target CTL against non-major histocompatibility complex antigens such as Ig, parasites and tumor-associated antigens.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Lanzavecchia A,Scheidegger Ddoi
10.1002/eji.1830170118subject
Has Abstractpub_date
1987-01-01 00:00:00pages
105-11issue
1eissn
0014-2980issn
1521-4141journal_volume
17pub_type
杂志文章abstract::The phosphodiesterase inhibitor oxpentifylline (OXP) has a number of potentially important immunomodulatory actions which include a selective inhibition of the Th1 subset of CD4+ cells in vitro and inhibition of tumor necrosis factor (TNF)-alpha mRNA transcription. In vivo, it has a dramatic protective effect against ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830251029
更新日期:1995-10-01 00:00:00
abstract::An anti-T cell receptor (TcR) monoclonal antibody (mAb), LC4, directed against a human leukemic T cell line, SUP-T13, caused DNA fragmentation ("apoptosis") and cell death upon binding to this cell line. Cross-linking of receptor molecules was necessary for this effect since F(ab')2, but not Fab', fragments of LC4 cou...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830191023
更新日期:1989-10-01 00:00:00
abstract::The diversity of the human immune repertoire and how it relates to a functional immune response has not yet been studied in detail in humanized NOD.SCID.gammac(-/-) immunodeficient mice. Here, we used a multiplex PCR on genomic DNA to quantify the combinatorial diversity of all possible V-J rearrangements at the TCR-b...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200939480
更新日期:2009-08-01 00:00:00
abstract::Cell suspensions enriched for N cells, the effector cell for human natural cell-mediated cytotoxicity, were observed to react strongly with a rabbit antiserum directed against an antigen associated with B cells. Treatment of the effector suspension with the antiserum resulted in inhibition of natural cell-mediated cyt...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830071016
更新日期:1977-10-01 00:00:00
abstract::The human monocyte line, U-937, derived from an individual with histiocytic lymphoma was studied for the expression of surface C3 receptors, after cultivation in the presence of phorbol myristate acetate (PMA) or T lymphocyte-conditioned medium. Receptors were detected by using EAC4b, EAC3b, EC3b, EAC3bi and EAC3d int...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830151005
更新日期:1985-10-01 00:00:00
abstract::The killer cell lectin-like receptor G1 (KLRG1) is a cadherin-binding inhibitory receptor expressed by NK cells and differentiated T cells. Here, we surprisingly found that a fraction of KLRG1 molecules expressed in the murine A5 T-cell line and in IL-2-activated NK cells forms disulfide-linked heteromers with the tra...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201344234
更新日期:2014-06-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV-specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV-infected lymphoblasts. Furthermore...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830190904
更新日期:1989-09-01 00:00:00
abstract::Levamisole, an anti-anergic chemotherapeutic agent, is shown to depress the azathioprine sensitivity of rosette-forming cells (RFC) in the spleen of normal mice, and to restore the azathioprine sensitivity of RFC in the spleen of adult thymectomized mice. Using the fully active dose of 1.25 mg/kg i.v., the restoration...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830060414
更新日期:1976-04-01 00:00:00
abstract::Precursor CD4-CD8- (DN) thymocytes rearrange their TCR-beta genes, and only those which succeed in beta-selection subsequently expand and differentiate into immature CD4+CD8+ (DP) thymocytes. The cell subsets corresponding to the successive steps of this transition can be defined in terms of CD44 and CD25 expression. ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(2001010)31:10<3038::aid-immu3038
更新日期:2001-10-01 00:00:00
abstract::NK cells can kill transformed, infected and stressed cells while most normal cells are spared. NK cells are activated by various endogenous self-ligands, some of which are actually expressed by normal cells. Thus, NK cells are inherently self-reactive and consequently, potentially auto-aggressive. How these cells are ...
journal_title:European journal of immunology
pub_type: 杂志文章,评审
doi:10.1002/eji.200838755
更新日期:2008-11-01 00:00:00
abstract::The poxvirus A39R protein is a member of the semaphorin family that binds to Plexin C1, a molecule expressed on neutrophils and dendritic cells (DC). We previously showed that binding of A39R to Plexin C1 induces local rearrangement of the actin cytoskeleton and inhibits integrin-mediated adhesion, leading to cell ret...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200425669
更新日期:2005-02-01 00:00:00
abstract::CD25+ FOXP3+CD4+ T cells (Treg) have been considered to play an important role in immune tolerance against several tumor antigens. It has also been indicated that high-level expression of FOXP3 (FOXP3high) is sufficient to confer suppressive activity to normal non-Treg. Here, we showed for the first time that vascular...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200939887
更新日期:2010-01-01 00:00:00
abstract::The induction of B cell tolerance to 2,4-dinitrophenyl conjugates of polysaccharide antigens (levan or dextran) was studied in mice primed with keyhole limpet hemocyanin (KLH) or 2,4,6-trinitrophenylated KLH. The relationship of the epitope density of the tolerogen with avidity of B cell receptors (as judged indirectl...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830060910
更新日期:1976-09-01 00:00:00
abstract::Development of Th1 and Th2 effector lymphocytes is driven primarily by IL-12 or IL-4, but is also influenced by the strength of antigenic stimulation. However, the mechanism by which TCR signaling contributes to T cell polarization remains elusive. We show that in the presence of IL-12 a short TCR stimulation can lead...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199912)29:12<4092::AID-IMM
更新日期:1999-12-01 00:00:00
abstract::A conditionally immortalized dendritic cell line was established from bone marrow of mice transgenic for a thermolabile mutant of the SV40 large T antigen under the control of the class I Kb promoter. At the permissive temperature of 33 degrees-37 degrees C, the line divides in the absence of granulocyte/macrophage co...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830261105
更新日期:1996-11-01 00:00:00
abstract::To investigate the role of membrane lymphotoxin (LT)alpha1 / beta2 and its LTbeta receptor (LTbetaR) in the protective immune response to Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection, we have used a soluble fusion molecule (LTbetaR-IgG1). LTbetaR-Ig treatment interferes with granuloma formation mainly ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(SICI)1521-4141(199912)29:12<4002::AID-IMM
更新日期:1999-12-01 00:00:00
abstract::Surfactant protein A (SP-A) and surfactant protein D (SP-D) are collectins, and both proteins were shown to interact with influenza A virus and alveolar macrophages. However, it is not known whether SP-A and SP-D can serve as opsonins for the phagocytosis of influenza A virus by alveolar macrophages. In the present st...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270413
更新日期:1997-04-01 00:00:00
abstract::The immune and endocrine systems ensure two vital functions in the body. The immune system protects us from lethal pathogens, whereas the endocrine system ensures proper metabolic function of peripheral organs by regulating systemic homeostasis. These two systems were long thought to operate independently. The immune ...
journal_title:European journal of immunology
pub_type: 杂志文章,评审
doi:10.1002/eji.201847895
更新日期:2019-07-01 00:00:00
abstract::CD4+ CD25+ Foxp3+ regulatory T cells (Treg) are natural suppressors of autoimmunity but they can also dampen the effective clearance of infectious organisms. These cells have the potential to be exploited to prevent transplant rejection and to treat autoimmune disease. A paper in this issue of the European Journal of ...
journal_title:European journal of immunology
pub_type: 评论,杂志文章,评审
doi:10.1002/eji.200635967
更新日期:2006-04-01 00:00:00
abstract::We have further characterized the in vitro phenotype and function of anergic and suppressive CD4(+)25(+) T cells. Following TCR ligation, DO.11.10 CD4(+)25(+) T cells suppress the activation of OT-1 CD8(+)25(-) T cells in an antigen nonspecific manner. Although suppression was seen when using a mixture of APC from bot...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200208)32:8<2365::AID-IMMU2365>3
更新日期:2002-08-01 00:00:00
abstract::The fate of the T cell receptor (TcR)/CD3 complex was examined on a cytotoxic T lymphocyte (CTL) clone (KB5.C20) activated either via binding of an anti-TcR monoclonal antibody (mAb) or by a Ca2+ ionophore and phorbol 12-myristate 13-acetate (PMA). After binding of the anti-TcR mAb, electron microscopy revealed intern...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830210707
更新日期:1991-07-01 00:00:00
abstract::Japanese encephalitis, caused by infection with the neurotropic flavivirus, Japanese encephalitis virus (JEV), is among the most important viral encephalitides in Asia. While previous studies established an essential role of Ab and type I IFN, it is still unclear if the cell-mediated immune responses, through their di...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.201243152
更新日期:2013-07-01 00:00:00
abstract::Transcriptional up-regulation of the VCAM-1 gene, induced by proinflammatory cytokines such as IL-1beta and TNF-alpha, requires activation of not only NF-kappaB, but also involves interferon regulatory factor (IRF)-1. During a study of gene induction by mechanical stimuli in cultured human endothelial cells, we noted ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/1521-4141(200207)32:7<1821::AID-IMMU1821>3
更新日期:2002-07-01 00:00:00
abstract::Human interdigitating dendritic cells (IDC) were isolated from tonsils based on their CD40+ lineage-negative expression in situ. Isolated IDC displayed a phenotypic profile similar to that of IDC in tonsils and spleen in situ, characterized by high-level expression of major histocompatibility complex class II, the co-...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830270531
更新日期:1997-05-01 00:00:00
abstract::The heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been described as an important autoantigen in rheumatoid arthritis (RA) since it is targeted by autoantibodies, autoreactive T cells, and is aberrantly expressed in synovial cells in patients. To identify hnRNP-A2-specific T-cell epitopes possibly associate...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200939482
更新日期:2010-06-01 00:00:00
abstract::We have followed the fate of mature CD8+ T cells with a male-specific transgenic T cell receptor after antigenic stimulation with hemopoietic cells in the absence or presence of help. Our data show that mature CD8+ T cells can be deleted after a 3-week period of transient activation and that help, e.g. in the form of ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830230835
更新日期:1993-08-01 00:00:00
abstract::The internalization and intracellular processing of monoclonal antibody to immunoglobulin mu heavy chain (Mamu) have been investigated in two human Burkitt lymphoma cell lines (Ramos and Raji), in a human B cell lymphoma and in normal human peripheral blood B cells. In addition to the degradation of 125I-labeled Mamu ...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830160314
更新日期:1986-03-01 00:00:00
abstract::Durch Pflanzenkrankheiten entstehen weltweit hohe Ernteverluste. Eine der häufigsten Infektionen in der Familie der Kreuzb&luml;tengewächse wird durch den Pilz Plasmodiophora brassicae verursacht. Die Krankheit äußert sich in Form von Wurzeltumoren, den "Kohlherniegallen". Da es auf verseuchten Böden zu hohen Ernteaus...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/(sici)1521-415x(200001)30:1<14::aid-biuz14
更新日期:2000-01-01 00:00:00
abstract::The adoptive transfer of CD4(+)CD25(+) natural regulatory T cells (Treg) is a promising strategy for the treatment of autoimmune diseases and the prevention of alloresponses after transplantation. Clinical trials exploring this strategy require efficient in vitro expansion of this rare cell population. Protocols devel...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.200838904
更新日期:2009-04-01 00:00:00
abstract::The invariant chain (Ii) binds to newly synthesized major histocompatibility complex (MHC) class II molecules and is targeted to an acidic compartment where it is degraded. To evaluate its role on the conformation and the subcellular distribution of murine MHC class II molecules we have established stable L cell trans...
journal_title:European journal of immunology
pub_type: 杂志文章
doi:10.1002/eji.1830231218
更新日期:1993-12-01 00:00:00