DOCSLIB.ORG

Cells + CD2/CD16-Dependent Apoptosis of CD2 Induces CD16

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cells + CD2/CD16-Dependent Apoptosis of CD2 Induces CD16 Alefacept, an Immunomodulatory Recombinant LFA-3/IgG1 Fusion Protein, Induces CD16 Signaling and CD2/CD16-Dependent Apoptosis of CD2 + This information is current as Cells of September 28, 2021. Antonio J. da Silva, Margot Brickelmaier, Gerard R. Majeau, Zhifang Li, Lihe Su, Yen-Ming Hsu and Paula S. Hochman J Immunol 2002; 168:4462-4471; ; doi: 10.4049/jimmunol.168.9.4462 Downloaded from http://www.jimmunol.org/content/168/9/4462 References This article cites 54 articles, 25 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/168/9/4462.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2002 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Alefacept, an Immunomodulatory Recombinant LFA-3/IgG1 Fusion Protein, Induces CD16 Signaling and CD2/CD16-Dependent Apoptosis of CD2؉ Cells1 Antonio J. da Silva,2 Margot Brickelmaier, Gerard R. Majeau, Zhifang Li, Lihe Su, Yen-Ming Hsu, and Paula S. Hochman Alefacept, an immunomodulatory recombinant fusion protein composed of the first extracellular domain of LFA-3 fused to the human IgG1 hinge, CH2, and CH3 domains, has recently been shown in phase II and III clinical trials to safely reduce disease expression in patients with chronic plaque psoriasis. Alefacept modulates the function of and selectively induces apoptosis of CD2؉ human memory-effector T cells in vivo. We have sought to gain further understanding of the mechanisms of action that influence the biological activity of alefacept and may contribute to its efficacy and patient responsiveness. Specifically evaluated is the ability Downloaded from of alefacept to activate intracellular signals mediated via CD2 and/or Fc␥RIII (CD16). Experimentation using isoforms of alefacept ␥ engineered to have amino acid substitutions in the IgG1 CH2 domain that impact Fc R binding indicate that alefacept mediates cognate interactions between cells expressing human CD2 and CD16 to activate cells, e.g., increase extracellular signal-regulated kinase phosphorylation, up-regulate cell surface expression of the activation marker CD25, and induce release of granzyme B. In the systems used, this signaling is shown to require binding to CD2 and CD16 and be mediated through CD16, but not CD2. Experimentation using human CD2-transgenic mice and isoforms of alefacept confirmed the requirement for Fc␥R binding for http://www.jimmunol.org/ detection of the pharmacological effects of alefacept in vivo. Thus alefacept acts as an effector molecule, mediating cognate ,interactions to activate Fc␥R؉ cells (e.g., NK cells) to induce apoptosis of sensitive CD2؉ target cells. The Journal of Immunology 2002, 168: 4462–4471. espite progress in the clinical development of mAbs and ment of indirect host effects, such as the release of inflammatory IgG fusion proteins as therapeutics, the mechanism(s) cytokines, immune regulation, Ag presentation, target cell death D contributing to their efficacy and patient responsiveness (e.g., complement-dependent cytotoxicity (necrosis) or Ab-depen- is still largely undefined (reviewed in Refs. 1 and 2). Although dent cell-mediated cytotoxicity (apoptosis)), endocytosis, and by guest on September 28, 2021 initial evaluations of Ig-based therapeutics focused on antagonism phagocytosis (4, 6). Moreover, engineering of IgG-based thera- or agonism of cellular processes mediated upon ligation of the peutics may address patient-specific factors, such as ligand or Fc targeted ligand, it is now apparent that the Fc regions of Ig-based receptor polymorphisms, which potentially may differ in control agents also may contribute to their biological activity (3, 4). Thus, and diseased populations and are likely to be reflected in thera- both regions may be engineered to enhance the therapeutics’ phar- peutic efficacy in vivo. This has been suggested for the therapeutic macokinetics and pharmacodynamics to maximize efficacy. More mAbs Herceptin and Rituxan (both from Genentech, South San specifically, chemical and genetic modifications can be made to Francisco, CA), specific for the signaling receptors c-erbB-2 and alter the specificity/affinity of binding: 1) to ligand on target cells CD20, respectively (10–12). Initially it was postulated that the (5) and 2) of the Ig Fc domains to complement, FcRn, and FcR therapeutic activities of these mAbs might derive solely from the (6–9). The three classes of differentially expressed IgG Fc recep- agonistic or antagonistic functions mediated upon binding of their tors are functionally of two types: the multimeric activation recep- complementarity-determining regions to their molecular target on ␥ ␥ tors Fc RI (CD64) and Fc RIII (CD16) comprised of both an cells. More recent data from experimental models suggest that the Fc-binding and a signaling subunit (the immunoreceptor tyrosine- molecular mechanism(s) underlying the biologic activities of Her- based activation motif), and a inhibitory receptor, monomeric ceptin and Rituxan (4) and alefacept, the CD2 receptor-specific Fc␥RII (CD32), containing an immunoreceptor tyrosine-based in- therapeutic LFA-3/IgG1 fusion protein (13, 14), may also reside hibitory motif (6). In this context rational design of the IgG Fc with IgG Fc-recruited host effector functions, including the acti- domains of therapeutics can thus select for or against the recruit- vation of apoptosis and Ig-dependent cellular cytotoxicity (e.g., ADCC). As such, clinical and experimental exploration of the rel- ative benefits of human Fc␥ isoforms of such therapeutic con- Biogen, Inc., Cambridge, MA 02142 structs that differ with regard to their ability to mediate effector Received for publication December 17, 2001. Accepted for publication February 27, 2002. functions are prescribed. The costs of publication of this article were defrayed in part by the payment of page Alefacept (human LFA-3/IgG1 fusion protein), previously re- charges. This article must therefore be hereby marked advertisement in accordance ferred to as LFA3TIP, is an immunomodulatory recombinant fu- with 18 U.S.C. Section 1734 solely to indicate this fact. sion protein composed of the first extracellular domain of LFA-3 1 Alefacept (human LFA-3/IgG1 fusion protein) is currently being developed under fused to the human IgG1 hinge, C 2, and C 3 domains (13). the brand name AMEVIVE (Biogen, Cambridge, MA). H H LFA-3 (CD58) is the primary physiologic ligand for human CD2 2 Address correspondence and reprint requests to Dr. Antonio J. da Silva, Biogen, Inc., 14 Cambridge Center, Cambridge, MA 02142. E-mail address: antonio_ and is expressed on many cell types, including APCs (reviewed in [email protected] Ref. 15). In contrast, human CD2 has a more restricted distribution, Copyright © 2002 by The American Association of Immunologists 0022-1767/02/$02.00 The Journal of Immunology 4463 being detected primarily on T cells and NK cells (reviewed in Ref. cDNA was generated by RT-PCR from RNA extracted from the CD16ϩ 16), with elevated expression noted on activated or memory-effector Jurkat cells (26). Cotransfections were conducted by electroporation of the CD45ROϩ T cells (17–19). Engagement of CD2 on responder T or CD16 construct with a vector carrying the neomycin resistance gene (pGX- N28) for positive selection. Stable transfectants were isolated and ex- NK cells by LFA-3 on accessory cells costimulates immune responses panded by selection with geneticin (G418 sulfate). The cells were then potentially by improving the avidity of cellular interactions or by me- sorted by FACS to isolate populations observed to be phenotypically diating activating signals in the responder cells (15, 16). Indeed, anti- CD2ϪCD3ϩCD16ϩ or CD2ϩCD3ϩCD16Ϫ. The expressed recombinant CD2 mAbs and soluble forms of LFA-3, including LFA-3/IgG1 fu- CD16 is expected to form a heterodimeric receptor complex with the TCR ␨-chain to allow for CD16-generated signaling cascades (6, 26). These cells sion proteins, have been shown to costimulate T cell activation and were transiently transfected with a reporter gene construct (NFAT-lucif- proliferation under certain experimental conditions (20, 21). Addition- erase; Clontech, Palo Alto, CA) and assayed as described below. ally, however, both alefacept and Abs specific for human CD2 and human LFA-3 have been shown to inhibit T cell activities in vitro and Fusion proteins in vivo (13, 14, 22). Recently, alefacept as a monotherapy has been Alefacept is composed of the first extracellular domain of LFA-3 fused to shown in phase II and III clinical trials to reduce disease expression the hinge, CH2 domain, and CH3 domain of human IgG1. Its construction, safely in patients with chronic plaque psoriasis (23) (M. Lebwohl, E. expression, and purification have been described previously (13). Con- Christophers, R. Langley, J.-P. Ortonne, J. Roberts, C. E. M. Griffiths, structs encoding fusion proteins identical with alefacept, but with muta- tions encoding amino acids substitutions at alefacept positions 106, 107, and the Alefacept Clinical Study Group, manuscript in preparation and 109, which correspond to amino acid positions 234, 235, and 237 and G. Krueger, K. Papp, D. Stough, K. Loven, W. Gulliver, C. Ellis, (according to European Union numbering) of the human IgG1 CH2 do- and the Alefacept Clinical Study Group, manuscript in preparation), main, or only at alefacept position 107 (amino acid 235 of human IgG1) consistent with reports that T cells are central to the underlying patho- were also prepared.
Load more

Recommended publications
  • Tools for Cell Therapy and Immunoregulation
    RnDSy-lu-2945 Tools for Cell Therapy and Immunoregulation Target Cell TIM-4 SLAM/CD150 BTNL8 PD-L2/B7-DC B7-H1/PD-L1 (Human) Unknown PD-1 B7-1/CD80 TIM-1 SLAM/CD150 Receptor TIM Family SLAM Family Butyrophilins B7/CD28 Families T Cell Multiple Co-Signaling Molecules Co-stimulatory Co-inhibitory Ig Superfamily Regulate T Cell Activation Target Cell T Cell Target Cell T Cell B7-1/CD80 B7-H1/PD-L1 T cell activation requires two signals: 1) recognition of the antigenic peptide/ B7-1/CD80 B7-2/CD86 CTLA-4 major histocompatibility complex (MHC) by the T cell receptor (TCR) and 2) CD28 antigen-independent co-stimulation induced by interactions between B7-2/CD86 B7-H1/PD-L1 B7-1/CD80 co-signaling molecules expressed on target cells, such as antigen-presenting PD-L2/B7-DC PD-1 ICOS cells (APCs), and their T cell-expressed receptors. Engagement of the TCR in B7-H2/ICOS L 2Ig B7-H3 (Mouse) the absence of this second co-stimulatory signal typically results in T cell B7-H1/PD-L1 B7/CD28 Families 4Ig B7-H3 (Human) anergy or apoptosis. In addition, T cell activation can be negatively regulated Unknown Receptors by co-inhibitory molecules present on APCs. Therefore, integration of the 2Ig B7-H3 Unknown B7-H4 (Mouse) Receptors signals transduced by co-stimulatory and co-inhibitory molecules following TCR B7-H5 4Ig B7-H3 engagement directs the outcome and magnitude of a T cell response Unknown Ligand (Human) B7-H5 including the enhancement or suppression of T cell proliferation, B7-H7 Unknown Receptor differentiation, and/or cytokine secretion.
    [Show full text]
  • CD2 Molecules Redistribute to the Uropod During T Cell Scanning: Implications for Cellular Activation and Immune Surveillance
    CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance Elena V. Tibaldi*†, Ravi Salgia†‡, and Ellis L. Reinherz*†§ *Laboratory of Immunobiology and ‡Division of Adult Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, and †Department of Medicine, Harvard Medical School, Boston, MA 02115 Communicated by Stuart F. Schlossman, Dana-Farber Cancer Institute, Boston, MA, April 9, 2002 (received for review February 14, 2002) Dynamic binding between CD2 and CD58 counter-receptors on op- cells, whereas its counter-receptor CD58 is expressed on a posing cells optimizes immune recognition through stabilization of diverse array of nucleated and non-nucleated cells including cell–cell contact and juxtaposition of surface membranes at a distance APCs and stromal cells (reviewed in refs. 11 and 12). CD2 suitable for T cell receptor–ligand interaction. Digitized time-lapse functions in both T cell adhesion and activation processes (13). Ϸ differential interference contrast and immunofluorescence micros- Of note, the weak affinity of the CD2-CD58 interaction (Kd copy on living cells now show that this binding also induces T cell 1 ␮M) is associated with remarkably fast on and off rates that polarization. Moreover, CD2 can facilitate motility of T cells along foster rapid and extensive exchange between CD2 and CD58 antigen-presenting cells via a movement referred to as scanning. Both partners on opposing cell surfaces (14–16). These biophysical activated CD4 and CD8 T cells are able to scan antigen-presenting cells characteristics are reminiscent of the selectin–ligand interactions surfaces in the absence of cognate antigen.
    [Show full text]
  • Folate Receptor Β Regulates Integrin Cd11b/CD18 Adhesion of a Macrophage Subset to Collagen
    Folate Receptor β Regulates Integrin CD11b/CD18 Adhesion of a Macrophage Subset to Collagen This information is current as Christian Machacek, Verena Supper, Vladimir Leksa, Goran of September 25, 2021. Mitulovic, Andreas Spittler, Karel Drbal, Miloslav Suchanek, Anna Ohradanova-Repic and Hannes Stockinger J Immunol 2016; 197:2229-2238; Prepublished online 17 August 2016; doi: 10.4049/jimmunol.1501878 Downloaded from http://www.jimmunol.org/content/197/6/2229 Supplementary http://www.jimmunol.org/content/suppl/2016/08/17/jimmunol.150187 Material 8.DCSupplemental http://www.jimmunol.org/ References This article cites 49 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/197/6/2229.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 25, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Folate Receptor b Regulates Integrin CD11b/CD18 Adhesion of a Macrophage Subset to Collagen Christian Machacek,* Verena Supper,* Vladimir Leksa,*,† Goran Mitulovic,‡ Andreas Spittler,x Karel Drbal,{,1 Miloslav Suchanek,{ Anna Ohradanova-Repic,* and Hannes Stockinger* Folate, also known as vitamin B9, is necessary for essential cellular functions such as DNA synthesis, repair, and methylation.
    [Show full text]
  • Response Gene Expression That Modulates T Cell Induces a Differential Cytokine Tuberculosis Mycobacterium Dendritic Cells with I
    Infection of Human Macrophages and Dendritic Cells with Mycobacterium tuberculosis Induces a Differential Cytokine Gene Expression That Modulates T Cell This information is current as Response of September 24, 2021. Elena Giacomini, Elisabetta Iona, Lucietta Ferroni, Minja Miettinen, Lanfranco Fattorini, Graziella Orefici, Ilkka Julkunen and Eliana M. Coccia J Immunol 2001; 166:7033-7041; ; Downloaded from doi: 10.4049/jimmunol.166.12.7033 http://www.jimmunol.org/content/166/12/7033 http://www.jimmunol.org/ References This article cites 51 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/166/12/7033.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 24, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Infection of Human Macrophages and Dendritic Cells with Mycobacterium tuberculosis Induces a Differential Cytokine Gene Expression That Modulates T Cell Response1 Elena Giacomini,* Elisabetta Iona,† Lucietta Ferroni,* Minja Miettinen,‡ Lanfranco Fattorini,† Graziella Orefici,† Ilkka Julkunen,‡ and Eliana M.
    [Show full text]
  • REVIEW Dendritic Cell-Based Vaccine
    Leukemia (1999) 13, 653–663 1999 Stockton Press All rights reserved 0887-6924/99 $12.00 http://www.stockton-press.co.uk/leu REVIEW Dendritic cell-based vaccine: a promising approach for cancer immunotherapy K Tarte1 and B Klein1,2 1INSERM U 475, Montpellier; and 2Unit For Cellular Therapy, CHU Saint Eloi, Montpellier, France The unique ability of dendritic cells to pick up antigens and to + + and interstitial DC pick up antigens (Ag) in peripheral tissues activate naive and memory CD4 and CD8 T cells raised the and migrate to lymphoid organs through lymphatic vessels in possibility of using them to trigger a specific anti-tumor 8 immunity. If numerous studies have shown a major interest in response to inflammatory stimuli. Activated mature DC, dendritic cell-based vaccines for cancer immunotherapy in ani- which express CD1a and CD83 antigens, represent the latter mal models, only a few have been carried out in human can- stage of LC and interstitial DC maturation. According to their cers. In this review, we describe recent findings in the biology high expression of MHC class I, MHC class II and costimu- of dendritic cells that are important to generate anti-tumor cyto- latory molecules, they present, efficiently, Ag-derived peptides toxic T cells in vitro and we also detail clinical studies reporting to CD4+ and CD8+ T lymphocytes in lymph node T cell areas the obtention of specific immunity to human cancers in vivo using reinfusion of dendritic cells pulsed with tumor antigens. (Figure 1). Recently, another subset of DC was identified on Keywords: dendritic cells; cancer; immunotherapy the basis of their high expression of the interleukin-3 receptor alpha chain (IL-3R␣hi).
    [Show full text]
  • The Role of the CD58 Locus in Multiple Sclerosis
    The role of the CD58 locus in multiple sclerosis Philip L. De Jagera,b,c,1, Clare Baecher-Allana, Lisa M. Maiera,c, Ariel T. Arthurd, Linda Ottobonia,c, Lisa Barcellose, Jacob L. McCauleyf, Stephen Sawcerg, An Gorish, Janna Saarelai, Roman Yelenskyc,j, Alkes Pricec,k, Virpi Leppai, Nick Pattersonc, Paul I. W. de Bakkerb,c, Dong Trana,c, Cristin Aubina,c, Susan Pobywajloa, Elizabeth Rossina,c, Xinli Huc, Charles W. Ashleya, Edwin Choyc,j, John D. Riouxc,l, Margaret A. Pericak-Vancef, Adrian Ivinsonm, David R. Boothn, Graeme J. Stewartn, Aarno Palotiec,h, Leena Peltonenc,h,Be´ ne´ dicte Duboisg, Jonathan L. Haineso, Howard L. Weinera, Alastair Compstong, Stephen L. Hauserp,q, Mark J. Dalyc,j, David Reichc,j, Jorge R. Oksenbergp,q, and David A. Haflera,c. aDivision of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; bPartners Center for Personalized Genetic Medicine, Boston, MA 02115; cProgram in Medical and Population Genetics, Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139; dDepartment of Medicine and the Nerve Research Foundation, University of Sydney, Sydney NSW 2145, Australia; eDivision of Epidemiology, School of Public Health, University of California, Berkeley, CA 94720-7360; fMiami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136; gDepartment of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge, Box 165, Hills Road, Cambridge CB2 2QQ,
    [Show full text]
  • Understanding the Synergy of Nkp46 and Co-Activating Signals in Various NK Cell Subpopulations: Paving the Way for More Successful NK-Cell-Based Immunotherapy
    cells Article Understanding the Synergy of NKp46 and Co-Activating Signals in Various NK Cell Subpopulations: Paving the Way for More Successful NK-Cell-Based Immunotherapy 1,2, 3, 1, 1 Loris Zamai * , Genny Del Zotto y , Flavia Buccella y, Sara Gabrielli , Barbara Canonico 1 , Marco Artico 4, Claudio Ortolani 1 and Stefano Papa 1 1 Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, 61032 Urbino, Italy; fl[email protected] (F.B.); [email protected] (S.G.); [email protected] (B.C.); [email protected] (C.O.); [email protected] (S.P.) 2 INFN-Gran Sasso National Laboratory, Assergi, 67100 L’Aquila, Italy 3 Area Aggregazione Servizi e Laboratori Diagnostici, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy; [email protected] 4 Department of Sensory Organs, Sapienza University of Rome, 00161 Rome, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-0722-304319; Fax: +39-0722-304319 These authors contributed equally. y Received: 11 February 2020; Accepted: 13 March 2020; Published: 19 March 2020 Abstract: The NK cell population is characterized by distinct NK cell subsets that respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK cell subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e., resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity.
    [Show full text]
  • The B7/BB1 Antigen Provides One of Several Costimulatory Signals for the Activation of CD4+ T Lymphocytes by Human Blood Dendritic Cells in Vitro
    Amendment history: Correction (April 1993) The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J W Young, … , R M Steinman, B Dupont J Clin Invest. 1992;90(1):229-237. https://doi.org/10.1172/JCI115840. Research Article T cells respond to peptide antigen in association with MHC products on antigen-presenting cells (APCs). A number of accessory or costimulatory molecules have been identified that also contribute to T cell activation. Several of the known accessory molecules are expressed by freshly isolated dendritic cells, a distinctive leukocyte that is the most potent APC for the initiation of primary T cell responses. These include ICAM-1 (CD54), LFA-3 (CD58), and class I and II MHC products. Dendritic cells also constitutively express the accessory ligand for CD28, B7/BB1, which has not been previously identified on circulating leukocytes freshly isolated from peripheral blood. Dendritic cell expression of both B7/BB1 and ICAM-1 (CD54) increases after binding to allogeneic T cells. Individual mAbs against several of the respective accessory T cell receptors, e.g., anti-CD2, anti-CD4, anti-CD11a, and anti-CD28, inhibit T cell proliferation in the dendritic cell-stimulated allogeneic mixed leukocyte reaction (MLR) by 40-70%. Combinations of these mAbs are synergistic in achieving near total inhibition. Other T cell-reactive mAbs, e.g., anti-CD5 and anti-CD45, are not inhibitory. Lymphokine secretion and blast transformation are similarly reduced when active accessory ligand-receptor interactions are blocked in the dendritic cell-stimulated allogeneic […] Find the latest version: https://jci.me/115840/pdf The B7/BB1 Antigen Provides One of Several Costimulatory Signals for the Activation of CD4+ T Lymphocytes by Human Blood Dendritic Cells In Vitro James W.
    [Show full text]
  • Immunology Focus Summer | 2006 Immunology FOCUS
    R&D Systems Immunology Focus summer | 2006 Immunology FOCUS Inside page 2 Signal Transduction: Kinase & Phosphatase Reagents page 3 Lectin Family page 4 Regulatory T Cells page 5 Natural Killer Cells page 6 Innate Immunity & Dendritic Cells page 7 Co-Stimulation/-Inhibition The B7 Family & Associated Molecules page 8 Proteome Profiler™ Phospho-Immunoreceptor Array ITAM/ITIM-Associated Receptors www.RnDSystems.com Please visit our website @ www.RnDSystems.com for product information and past issues of the Focus Newsletter: Cancer, Neuroscience, Cell Biology, and more. Quality | Selec tion | Pe rformance | Result s Cancer Development Endocrinology Immunology Neuroscience Proteases Stem Cells Signal Transduction: Kinase & Phosphatase Reagents Co-inhibitory PD-L2/PD-1 signaling & SHP-2 phosphatase KINASE & PHOSPHATASE RESEARCH REAGENTS Regulation of MAP kinase (MAPK) signaling Kinases Phosphatases pathways is critical for T cell development, MOLECULE ANTIBODIES ELISAs/ASSAYS MOLECULE ANTIBODIES ELISAs/ASSAYS activation, differentiation, and death. MAPKs Akt Family H M R H M R Alkaline Phosphatase* H M R are activated by the dual phosphorylation of threonine and tyrosine residues resulting in AMPK H M R Calcineurin A, B H M R subsequent transcription factor activation. ATM H M R H CD45 H M H M The MAPK signaling pathway in T cells can be CaM Kinase II Ms CDC25A, B* H M R triggered by cytokines, growth factors, and CDC2 H M R DARPP-32 M R ligands for transmembrane receptors. Chk1, 2 H M R H M R DEP-1/CD148* H M R H Ligation of the T cell receptor (TCR)/CD3 ERK1, 2 H M R H M R LAR H M R complex results in rapid activation of PI 3- kinase, which leads to Akt and MAPK ERK3 H Lyp H activation.
    [Show full text]
  • Gene CD58 Human Basis for Alternative Mrna Splicing of The
    Gene Structure, Promoter Characterization, and Basis for Alternative mRNA Splicing of the Human CD58 Gene This information is current as Reinhard Wallich, Christiane Brenner, Yvonne Brand, Matthias of September 23, 2021. Roux, Manuel Reister and Stefan Meuer J Immunol 1998; 160:2862-2871; ; http://www.jimmunol.org/content/160/6/2862 Downloaded from References This article cites 60 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/160/6/2862.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 23, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Gene Structure, Promoter Characterization, and Basis for Alternative mRNA Splicing of the Human CD58 Gene1 Reinhard Wallich,2 Christiane Brenner, Yvonne Brand, Matthias Roux, Manuel Reister, and Stefan Meuer The 60-kDa lymphocyte function-associated Ag-3 (LFA-3/CD58), a highly glycosylated adhesion molecule that serves as ligand for the T cell-restricted glycoprotein CD2, is encoded by a gene at the human chromosome locus 1p13.
    [Show full text]
  • Resting Peripheral Blood B Cells Presentation of Immune Complexes
    Complement Opsonization Is Required for Presentation of Immune Complexes by Resting Peripheral Blood B Cells This information is current as Susan A. Boackle, Margaret A. Morris, V. Michael Holers of September 25, 2021. and David R. Karp J Immunol 1998; 161:6537-6543; ; http://www.jimmunol.org/content/161/12/6537 Downloaded from References This article cites 42 articles, 29 of which you can access for free at: http://www.jimmunol.org/content/161/12/6537.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 25, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Complement Opsonization Is Required for Presentation of Immune Complexes by Resting Peripheral Blood B Cells1 Susan A. Boackle,* Margaret A. Morris,† V. Michael Holers,* and David R. Karp2† Complement receptor 2 (CD21, CR2) is a B cell receptor for complement degradation products bound to Ag or immune complexes.
    [Show full text]
  • Characterisation of Chicken OX40 and OX40L
    Characterisation of chicken OX40 and OX40L von Stephanie Hanna Katharina Scherer Inaugural-Dissertation zur Erlangung der Doktorw¨urde der Tier¨arztlichenFakult¨at der Ludwig-Maximilians-Universit¨atM¨unchen Characterisation of chicken OX40 and OX40L von Stephanie Hanna Katharina Scherer aus Baunach bei Bamberg M¨unchen2018 Aus dem Veterin¨arwissenschaftlichenDepartment der Tier¨arztlichenFakult¨at der Ludwig-Maximilians-Universit¨atM¨unchen Lehrstuhl f¨urPhysiologie Arbeit angefertigt unter der Leitung von Univ.-Prof. Dr. Thomas G¨obel Gedruckt mit Genehmigung der Tier¨arztlichenFakult¨at der Ludwig-Maximilians-Universit¨atM¨unchen Dekan: Univ.-Prof. Dr. Reinhard K. Straubinger, Ph.D. Berichterstatter: Univ.-Prof. Dr. Thomas G¨obel Korreferenten: Priv.-Doz. Dr. Nadja Herbach Univ.-Prof. Dr. Bernhard Aigner Prof. Dr. Herbert Kaltner Univ.-Prof. Dr. R¨udiger Wanke Tag der Promotion: 27. Juli 2018 Meinen Eltern und Großeltern Contents List of Figures 11 Abbreviations 13 1 Introduction 17 2 Fundamentals 19 2.1 T cell activation . 19 2.1.1 The activation of T cells requires the presence of several signals 19 2.1.2 Costimulatory signals transmitted via members of the im- munoglobulin superfamily . 22 2.1.3 Costimulatory signals transmitted via members of the cy- tokine receptor family . 23 2.1.4 Costimulatory signals transmitted via members of the tumour necrosis factor receptor superfamily . 24 2.2 The tumour necrosis factor receptor superfamily . 26 2.2.1 The structure of tumour necrosis factor receptors . 26 2.2.2 Functional classification of TNFRSF members . 28 2.3 The tumour necrosis factor superfamily . 29 2.3.1 The structure of tumour necrosis factor ligands .
    [Show full text]