DOCSLIB.ORG

Structural Motifs for Recognition and Adhesion in Members of the Immunoglobulin Superfamily

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Structural Motifs for Recognition and Adhesion in Members of the Immunoglobulin Superfamily Journal of Cell Science 107, 2065-2070 (1994) 2065 Printed in Great Britain © The Company of Biologists Limited 1994 COMMENTARY Structural motifs for recognition and adhesion in members of the immunoglobulin superfamily Claire L. Holness and David L. Simmons* Cell Adhesion Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK *Author for correspondence INTRODUCTION The Ig domain found in recognition/adhesion molecules conforms to the β barrel plan. Compared with antibody V The immunoglobulin superfamily is the most abundant family domains, adhesion domains seem to have longer β strands and of cell surface molecules, accounting for 50% of leukocyte shorter connecting loop regions. The antigen-combining site of surface glycoproteins. This evolutionary success story is antibodies consists of the CDR (complementarity determining thought to be due to the stability of the Ig domain, which is regions) 1, 2 and 3, which are largely made from connecting able to resist the harsh proteolytic and oxidative environment loops. In contrast, adhesion binding surfaces seem to be made of the extracellular world. By mutation and selection, the Ig from the β strands themselves, arranged in flat faces. This is, domain has evolved to serve many different functions of course, a simplification and exceptions exist for both cases; including: receptors for growth factors (CSF-1 receptor, PDGF for antibodies the precise shape of the framework region of β receptor, FGF receptors); receptors for the Fc region of Ig (IgG strands is key to the organisation of the CDR loop regions. The receptors; CD16, CD32, CD64; CD89 IgA receptor); and as CDRs are not completely autonomous units; witness the trials adhesion molecules, which now seems to be the function of the of those presently engaged in humanising antibodies and gen- majority (CD2/CD58, CD28 and CTLA4, which bind to B7 erating in vitro antibody repertoires. For adhesion molecules, and B70; CD4/class II, CD8/class I, CD31/CD31, CD50 there are exceptions to the dominance of β strand face inter- (ICAM-3)/LFA-1, CD54 (ICAM-1)/LFA-1, CD102 (ICAM- actions, as some key residues involved in adhesion binding 2)/LFA-1, CD106 (VCAM)/VLA-4, NCAM/NCAM. L1, sites have been found in loops. MAG, TAG-1, CEA) (Springer, 1990). The packing and orientation of domains in adhesion The ideas and conventions defining the domain organisation molecules seems to be remarkably uniform. The contiguous Ig of this family were established by Alan Williams and Neil domains are arranged as an extended rod, with only small Barclay in a series of papers in the late 80s (Williams and angles of pitch between adjacent domains. For example, there Barclay, 1988; Williams et al., 1989). The basic Ig domain is is a common packing arrangement of domains 1 and 2 of CD2 built from a tightly packed barrel of β strands, either 7 strands and CD4, which is quite different from that seen in antibodies. in C1 and C2 domains (arranged in 2 layers of 3 and 4 strands So far, no antibody-like pattern, with heavy chain V domain designated ABE and CC′FG, respectively) or 9 strands in V bent at 90° to the contiguous CH1 domain, has been found. domains (arranged in two layers of 4 and 5 designated ABDE Although adhesin domains exist as an extended array, large and CC′C′′FG, respectively). There have been several recent rotational displacements between adjacent domains have been structural studies on adhesion molecules of the IgSF, including seen in the solved crystal structures of both CD2 and CD4 CD2 (solution NMR, Driscoll et al., 1991; Withka et al., 1993; (Jones et al., 1992; Ryu et al., 1990) and in the proposed model and crystallography at 2.8 Å resolution, Jones et al., 1992), CD4 for the N-terminal domains of ICAM-1 (Berendt et al., 1992). domains 1-2 (crystallography at 2.6 Å resolution, Garrett et al., For all these molecules adjacent domains are rotated by 160- 1993; Ryu et al., 1990; Wang et al., 1990) and domains 3-4 180° relative to each other. (crystallography at 2.8 Å resolution; Brady et al., 1993); the However, in spite of the common gross organisation of IgSF single V domain of CD8 (crystallography at 2.6 Å resolution; adhesins, there is a surprising diversity of modes of interaction Leahy et al., 1992); class II (crystallography at 2.8 Å resolu- amongst individual members. Fortunately, however, they can tion; Brown et al., 1993). In addition there have been extensive be grouped into a small number of patterns: (1) heterotypic mutagenesis screens of Ig domains involved in adhesion binding mediated by the N-terminal Ig domain(s); (2) including: CD2, which binds CD58 (LFA-3) (Somoza et al., homotypic binding mediated by ‘internal’ domain(s) and 1993; Arulanandam et al., 1993); CD4, which binds class II requiring anti-parallel alignment of interdigitated molecules. (Moebius et al., 1993); ICAM-1, which bind LFA-1 (Staunton et al., 1990; Berendt et al., 1992); and VCAM-1, which binds VLA-4 (Osborn et al., 1994; Vonderheide et al., 1994). Key words: Ig superfamily, adhesion, binding site 2066 C. L. Holness and D. L. Simmons Although the focus of this Commentary will be IgSF Key to symbols in all Figs: members involved in adhesion/recognition, the Ig fold has also evolved to bind small ligands such as growth factors. Some of Basic immunoglobulin related domain the recent work mapping their binding sites, which tend to be discrete binding pockets in internal domains, will be discussed. Type III fibronectin related domain α1 and β1 peptide binding domains of class II HETEROTYPIC CAMs AND THE DOMINANCE OF D1 Binding sites and surfaces within domains The most detailed molecular picture of IgSF domain recogni- tion comes from heterotypic interactions involving leukocyte Tyrosine kinase domain CAMs; specifically CD2/CD58 CD4/class II and ICAM- 1/LFA-1. Combinations of mutagensis screens with modelling A and/or structural analysis have localised binding sites to par- CD2 CD2/CD58 ticular domains, faces and key residues. The results indicate that in these receptor/ligand pairs, the IgSF binding surface is D2 D1 localised to one face, the CFG face, and key residues are located within that face and at its edges (Fig. 1). A general model for how IgSF domains of adhesion molecules interact CFG face was proposed by Springer (1991) based on the NMR structure and mutagenesis studies of CD2, and the precedent of how the domains of antibody molecules pack together. ICAM-1 (CD54) For human CD2, residues clustered in the β strands C (K34 B D5 D4 D3 D2 D1 and E36) and C′ (R48 and K49) and also charged residues in AAA the connecting loop between the F and G strands (K91 and AAA N92) have been shown to be critical in this interaction (Somoza AAA et al., 1993; Arulanandam et al., 1993). Similarly located AAA charged residues have been identified as key components of Mac-1 LFA-1 the binding site on ICAMs 1 and 3 for the leukocyte integrin LFA-1. For human ICAM-1 and ICAM-3, residues E37 (E34, ICAM-3 (CD50) ICAM-1) in the CC′ strand and Q75 (Q72, ICAM-1) within D5 D4 D3 D2 D1 domain 1 of ICAMs-1 and 3 are essential components of the LFA-1 binding site (Staunton et al., 1990; Fawcett et al., 1992; Vazeux et al., 1992; de Fougerolles et al., 1993; Holness et al., unpublished data). In addition, Li et al. (1993) have defined a peptide from domain 1 of ICAM-2 (covering residues 21-42; LFA-1 Staunton et al., 1989a), which inhibits binding of ICAM-2 to β ′ LFA-1. This peptide encompasses strands B, C and C and Class II dimer thus confirms the importance of this region for all the ICAMs C as they interact with LFA-1. The key residues, E34 and Q73, are conserved across species and are present in chimpanzee CD4 AAAAAAAA ICAM-1 (Hammond and McClelland 1993), rat ICAM-1 (Kita AAAAAAAA et al., 1992), mouse ICAM-1 (Horley et al., 1989) and mouse AAAAAAAA ICAM-2 (Xu et al., 1992). Indeed, this motif may be generally important for the inter- action of integrins with members of the immunoglobulin super- family (IgSF). To date, there are three examples of Class II dimer IgSF/integrin interactions: ICAMs with LFA-1 and/or Mac-1 (Simmons et al., 1988; Staunton et al., 1988, 1989a; Diamond Fig. 1. Binding sites in heterotypic CAMs. (A) CD2, and the interaction of CD2 with CD58; (B) ICAMs 1 and 3; (C) CD4 et al., 1991); VCAM with VLA-4 (α4β1) and α4β7 integrins (Osborn et al., 1992; Elices et al., 1990; Ruegg et al., 1992); interacting with a dimer of MHC class II molecules. and MadCAM-1 with the α4β7 integrin (Berlin et al., 1993). A tripeptide motif LDV containing a charged residue (D) at an ICAM-1 can also bind to the major group of human rhi- equivalent location on the adhesion domains of VCAM-1 (D1 noviruses and to an unidentified receptor expressed on the and D4) (i.e. within the C-C′ loop region) is also important for surface of Plasmodium falciparum-infected erythrocytes. In binding to its cognate integrin VLA-4 (α4β1), (Osborn et al., both cases the interaction surfaces are distinctly different from 1994; Vonderheide et al., 1994; and John Clements, British Bio- the LFA-1 binding face. ICAM-1 is thought to fit into a deep technology, personal communication). Thus, a structural motif canyon on the surface of the rhinovirus and the binding site consisting of two elements, an acidic residue (either D or E) encompasses a large area of the ICAM (Staunton et al., 1989b, located in a CC′ loop and additional residues in the FG loop 1990).
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]
  • Human N-Cadherin / CD325 / CDH2 Protein (His & Fc Tag)
    Human N-Cadherin / CD325 / CDH2 Protein (His & Fc Tag) Catalog Number: 11039-H03H General Information SDS-PAGE: Gene Name Synonym: CD325; CDHN; CDw325; NCAD Protein Construction: A DNA sequence encoding the human CDH2 (NP_001783.2) (Met 1-Ala 724) was fused with the C-terminal polyhistidine-tagged Fc region of human IgG1 at the C-terminus. Source: Human Expression Host: HEK293 Cells QC Testing Purity: > 70 % as determined by SDS-PAGE Endotoxin: Protein Description < 1.0 EU per μg of the protein as determined by the LAL method Cadherins are calcium dependent cell adhesion proteins, and they preferentially interact with themselves in a homophilic manner in Stability: connecting cells. Cadherin 2 (CDH2), also known as N-Cadherin (neuronal) (NCAD), is a single-pass tranmembrane protein and a cadherin containing ℃ Samples are stable for up to twelve months from date of receipt at -70 5 cadherin domains. N-Cadherin displays a ubiquitous expression pattern but with different expression levels between endocrine cell types. CDH2 Asp 160 Predicted N terminal: (NCAD) has been shown to play an essential role in normal neuronal Molecular Mass: development, which is implicated in an array of processes including neuronal differentiation and migration, and axon growth and fasciculation. The secreted recombinant human CDH2 is a disulfide-linked homodimeric In addition, N-Cadherin expression was upregulated in human HSC during protein. The reduced monomer comprises 813 amino acids and has a activation in culture, and function or expression blocking of N-Cadherin predicted molecular mass of 89.9 kDa. As a result of glycosylation, it promoted apoptosis. During apoptosis, N-Cadherin was cleaved into 20- migrates as an approximately 114 and 119 kDa band in SDS-PAGE under 100 kDa fragments.
    [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]
  • L-Selectin/CD62L Is a Key Driver of Non-Alcoholic Steatohepatitis in Mice and Men
    cells Article L-Selectin/CD62L Is a Key Driver of Non-Alcoholic Steatohepatitis in Mice and Men Hannah K. Drescher 1,2,* , Angela Schippers 3, Stefanie Rosenhain 4 , Felix Gremse 4, Laura Bongiovanni 5 , Alain de Bruin 5, Sreepradha Eswaran 3, Suchira U. Gallage 6, Dominik Pfister 6, Marta Szydlowska 6, Mathias Heikenwalder 6, Sabine Weiskirchen 7, Norbert Wagner 3, Christian Trautwein 1, Ralf Weiskirchen 7 and Daniela C. Kroy 1 1 Department of Internal Medicine III, University Hospital, RWTH Aachen, 52074 Aachen, Germany; [email protected] (C.T.); [email protected] (D.C.K.) 2 Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA 3 Department of Pediatrics, University Hospital, RWTH Aachen, 52074 Aachen, Germany; [email protected] (A.S.); [email protected] (S.E.); [email protected] (N.W.) 4 Institute for Experimental Molecular Imaging, University Hospital, RWTH Aachen University, 52074 Aachen, Germany; [email protected] (S.R.); [email protected] (F.G.) 5 Dutch Molecular Pathology Centre, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3508 Utrecht, The Netherlands; [email protected] (L.B.); [email protected] (A.d.B.) 6 Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), 69120 Heidelberg, Germany; [email protected] (S.U.G.); dominik.pfi[email protected] (D.P.); [email protected] (M.S.); [email protected] (M.H.)
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • The Role of Fc Gamma Receptors in the Activity of Therapeutic Monoclonal Antibodies
    UNIVERSITY OF SOUTHAMPTON FACULTY OF MEDICINE Cancer Sciences Unit Volume 1 of 1 The Role of Fc Gamma Receptors in the Activity of Therapeutic Monoclonal Antibodies by Robert James Oldham Thesis for the degree of Doctor of Philosophy September 2016 UNIVERSITY OF SOUTHAMPTON ABSTRACT FACULTY OF MEDICINE Biomedicine Thesis for the degree of Doctor of Philosophy THE ROLE OF FC GAMMA RECEPTORS IN THE ACTIVITY OF THERAPEUTIC MONOCLONAL ANTIBODIES Robert James Oldham Fc gamma receptors (FcγRs) are the major family of receptors responsible for interacting with immunoglobulin G (IgG). They are known to be required for the anti-tumour activity of direct targeting mAbs through expression on NK cells and macrophages. Furthermore, recent work has suggested that cross-linking via FcγRs is required for the activity of agonistic, immune modulatory mAb. This thesis sought to investigate the requirement for these receptors for different aspects of mAb activity; from T cell activation to tumour depletion, using a combination of in vitro and in vivo systems. A panel of CHO-K1 cells were generated and transfected to express the polymorphic variants of human FcγRs. These were characterised for their ability to bind IgG before being used as feeder cells in T cell proliferation assays. The assays found that cross-linking of the anti-CD28 mAb, TGN1412 by FcγRIIb (CD32b) or FcγRIIa (CD32a) but not FcγRIIIa (CD16a) transfected cells induced T cell proliferation. Furthermore, this was accompanied by the release of pro-inflammatory cytokines including TNF-α, IFN-γ and IL-2. With the importance of cross-linking via CD32b demonstrated, experiments probed the mechanism of expression using Ramos and Raji cells.
    [Show full text]
  • Cell Adhesion and Angiogenesis
    Cell adhesion and angiogenesis. J Bischoff J Clin Invest. 1997;99(3):373-376. https://doi.org/10.1172/JCI119168. Perspective Find the latest version: https://jci.me/119168/pdf Perspectives Series: Cell Adhesion in Vascular Biology Cell Adhesion and Angiogenesis Joyce Bischoff Department of Surgery, Children’s Hospital and Harvard Medical School, Children’s Hospital, Boston, Massachusetts 02115 Introduction and postcapillary venules (3). Thus, the formation of a new mi- Angiogenesis is the growth of new capillary blood vessels from crovessel requires a number of interactions that must be coor- preexisting capillaries and postcapillary venules. This process dinated in a spatially and temporally specified manner. These is critical for normal growth and development and in protec- adhesion events are likely mediated by endothelial cell adhe- tive responses such as wound healing and inflammation. In sion molecules and ECM molecules that provide instructions healthy adults, angiogenesis does not normally occur except in to the endothelial cells as they migrate into the perivascular certain phases of the female reproductive cycle. However, ab- space and assemble into new vessels with surrounding peri- errant angiogenesis can occur in a variety of pathologic set- cytes. tings. These include the neovascularization of solid tumors, the Cell adhesion and endothelial cell growth growth of vessels into the retina in diabetic retinopathy, and the unwanted vessel growth in chronic inflammatory diseases. Adhesion of endothelial cells to ECM and attainment of an The hypothesis that angiogenic diseases, in particular tumor appropriate cellular shape has been known for many years to growth and metastases, may be alleviated by inhibiting the an- be crucial for endothelial cell growth, differentiation, and sur- giogenic responses (1) has prompted many to investigate the vival.
    [Show full text]
  • L1 Cell Adhesion Molecule in Cancer, a Systematic Review on Domain-Specific Functions
    International Journal of Molecular Sciences Review L1 Cell Adhesion Molecule in Cancer, a Systematic Review on Domain-Specific Functions Miriam van der Maten 1,2, Casper Reijnen 1,3, Johanna M.A. Pijnenborg 1,* and Mirjam M. Zegers 2,* 1 Department of Obstetrics and Gynaecology, Radboud university medical center, 6525 GA Nijmegen, The Netherlands 2 Department of Cell Biology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, 6525 GA Nijmegen, The Netherlands 3 Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands * Correspondence: [email protected] (J.M.A.P); [email protected] (M.M.Z.) Received: 24 June 2019; Accepted: 23 August 2019; Published: 26 August 2019 Abstract: L1 cell adhesion molecule (L1CAM) is a glycoprotein involved in cancer development and is associated with metastases and poor prognosis. Cellular processing of L1CAM results in expression of either full-length or cleaved forms of the protein. The different forms of L1CAM may localize at the plasma membrane as a transmembrane protein, or in the intra- or extracellular environment as cleaved or exosomal forms. Here, we systematically analyze available literature that directly relates to L1CAM domains and associated signaling pathways in cancer. Specifically, we chart its domain-specific functions in relation to cancer progression, and outline pre-clinical assays used to assess L1CAM. It is found that full-length L1CAM has both intracellular and extracellular targets, including interactions with integrins, and linkage with ezrin. Cellular processing leading to proteolytic cleavage and/or exosome formation results in extracellular soluble forms of L1CAM that may act through similar mechanisms as compared to full-length L1CAM, such as integrin-dependent signals, but also through distinct mechanisms.
    [Show full text]
  • CDH1 Gene Cadherin 1
    CDH1 gene cadherin 1 Normal Function The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body, such as the inside of the eyelids and mouth. E-cadherin belongs to a family of proteins called cadherins whose function is to help neighboring cells stick to one another (cell adhesion) to form organized tissues. Another protein called p120-catenin, produced from the CTNND1 gene, helps keep E-cadherin in its proper place in the cell membrane, preventing it from being taken into the cell through a process called endocytosis and broken down prematurely. E-cadherin is one of the best-understood cadherin proteins. In addition to its role in cell adhesion, E-cadherin is involved in transmitting chemical signals within cells, controlling cell maturation and movement, and regulating the activity of certain genes. Interactions between the E-cadherin and p120-catenin proteins, in particular, are thought to be important for normal development of the head and face (craniofacial development), including the eyelids and teeth. E-cadherin also acts as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. Health Conditions Related to Genetic Changes Breast cancer Inherited mutations in the CDH1 gene increase a woman's risk of developing a form of breast cancer that begins in the milk-producing glands (lobular breast cancer). In many cases, this increased risk occurs as part of an inherited cancer disorder called hereditary diffuse gastric cancer (HDGC) (described below).
    [Show full text]
  • Endothelial Venules in a Mucosal Site in Naive Lymphocyte Adhesion to High Primary Role of Peripheral Node Addressin Phenotypic
    Nasal-Associated Lymphoid Tissue: Phenotypic and Functional Evidence for the Primary Role of Peripheral Node Addressin in Naive Lymphocyte Adhesion to High This information is current as Endothelial Venules in a Mucosal Site of October 1, 2021. Keri L. Csencsits, Mark A. Jutila and David W. Pascual J Immunol 1999; 163:1382-1389; ; http://www.jimmunol.org/content/163/3/1382 Downloaded from References This article cites 50 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/163/3/1382.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on October 1, 2021 *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 © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Nasal-Associated Lymphoid Tissue: Phenotypic and Functional Evidence for the Primary Role of Peripheral Node Addressin in Naive Lymphocyte Adhesion to High Endothelial Venules in a Mucosal Site1 Keri L. Csencsits, Mark A. Jutila, and David W.
    [Show full text]