Role of Glycoproteins of the Immune and Blood Coagulation Systems

  • Inka Brockhausen
  • William Kuhns
Part of the Medical Intelligence Unit book series (MIU.LANDES)


Immunoglobulins and immunoglobulin-like cell surface domains are the most pervasive structures of the immune system. The latter group comprises over 70 members of the immunoglobulin superfamily which control cell behavior by acting as matrix binders, intercellullar adhesion molecules and/or signal transducing molecules. Many glycoproteins are found on the surfaces of cells of the immune system and their functions may be greatly influenced by glycosylation.1 For example, terminal sialic acid on lymphocytes helps to maintain normal homing patterns to tissues and organs; this function is altered following treatment of cells with neuraminidase.2 Neuraminidase also greatly reduces the colony forming ability of bone marrow stem cells.’ Selectin-mediated adhesion of leukocytes and tumor cells expressing sialyl Lex to endothelium is believed to antecede cell migration to ectopic sites of inflammation.4


Natural Killer Cell Sialic Acid Blood Group Blood Group Antigen High Mannose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Dustin ML, Staunton DE, Springer TA. Supergene families meet in the immune system. Immunol Today 1988; 9: 213–215.PubMedCrossRefGoogle Scholar
  2. 2.
    Gesner B, Ginsburg V. Effect of glycosidases on the fate of transfused lymphocytes. Proc Natl Acad Sci USA 1964; 52: 750–755.PubMedCrossRefGoogle Scholar
  3. 3.
    Tonelli Q, Meints R. Sialic acid:a specific role in hematopoietic spleen colony formation. J Supramolec Struct 1978; 8: 67–78.CrossRefGoogle Scholar
  4. 4.
    Hakomori S. Le x and related structures as adhesion molecules. Histochem J 1992; 24: 771–776.PubMedCrossRefGoogle Scholar
  5. 5.
    Keppler 0, Moldenhauer G, Oppenländer M et al. Human Golgi ß-galactoside a-2–6sialyltransferase generates a group of sialylated B lymphocyte differentiation antigens. Eur J Immun 1992; 22: 2777–2781.CrossRefGoogle Scholar
  6. 6.
    Braesch-Andersen S, Stamenkovic I. Sialylation of the B lymphocyte molecule CD22 by a2,6sialyltransferase is implicated in the regulation of CD22-mediated adhesion. J Biol Chem 1994; 269: 11783–11786.PubMedGoogle Scholar
  7. 7.
    Karasuno T, Kanayama Y, Nishiura T et al. Glycosidase inhibitors (castanospermine and swainsonine) and neuraminidase inhibit pokeweed mitogen-induced B cell maturation. Eur J Immun 1992; 22: 2003–2008.CrossRefGoogle Scholar
  8. 8.
    Recny M, Luther M, Knoppers M et al. Nglycosylation is required for human CD2 immunoadhesion functions. J Biol Chem 1992; 267: 22428–22434.PubMedGoogle Scholar
  9. 9.
    Withka J, Wyss D, Wagner G et al. Structure of the glycosylated adhesion domain of human T lymphocyte glycoprotein CD2. Curr Biol 1993; 1: 69–81.Google Scholar
  10. 10.
    Narasimhan S, Lee J, Cheung R et al. ß1,4-mannosyl glycoprotein ß-1,4-N-acetylglucosaminyl transferase III in human B and T lymphocyte lines and in tonsillar B and T lymphocytes. Biochem Cell Biol 1988; 66: 889–900.PubMedCrossRefGoogle Scholar
  11. 11.
    Lemaire S, Derappe C, Michalski J et al. Expression of 131–6 branched N-linked oligosaccharides is associated with activation in human T4 and T8 cell populations. J Biol Chem 1994; 269: 8069–8074.PubMedGoogle Scholar
  12. 12.
    Carlsson S. Changes in glycan branching and sialylation of the Thy-1 antigen during normal differentiation of mouse T lymphocytes. Biochem J 1985; 226: 519–525.PubMedGoogle Scholar
  13. 13.
    Carlsson S, Sasaki H, Fukuda M. Structural variations of 0-linked oligosaccharides present in leukosialin isolated from erythroid, myeloid, and T-lymphoid cell lines. J Biol Chem 1986; 261: 12787–12795.PubMedGoogle Scholar
  14. 14.
    Fukuda M. Leukosialin, a major 0-glycancontaining sialoglycoprotein defining leukocyte differentiation and malignancy. Glycobiology 1991; 1: 347–356.PubMedCrossRefGoogle Scholar
  15. 15.
    Ellies L, Jones A, Williams M et al. Differential regulation of CD43 glycoforms on CD4 and CD8 lymphocytes in graft versus host disease. Glycobiology 1994; 4: 885–893.PubMedCrossRefGoogle Scholar
  16. 16.
    Piller F, Piller V, Fox R et al. Human T lymphocyte activation is associated with changes in 0-glycan biosynthesis. J Biol Chem 1988; 263: 15146–15150.PubMedGoogle Scholar
  17. 17.
    Higgins E, Siminovitch K, Zhuang D et al. Aberrant 0-linked oligosaccharide biosynthesis in lymphocytes and platelets from patients with the Wiskott-Aldrich syndrome. J Biol Chem 1991; 266: 6280–6290.PubMedGoogle Scholar
  18. 18.
    Piller F, Le Deist F, Weinberg KI et al. Altered 0-glycan synthesis in lymphocytes from patients with Wiscott-Aldrich syn- drome. J Exp Med 1991; 173: 1501–1510.PubMedCrossRefGoogle Scholar
  19. 19.
    Mentzer S, Remold-O’Donnell E, Crimmins M et al. Sialophorin, a surface sialoglycoprotein defective in the WiskottAldrich syndrome, is involved in T-lymphocyte proliferation. J Exp Med 1987; 165: 1383–1392.PubMedCrossRefGoogle Scholar
  20. 20.
    Pimlott N, Miller R. Glycopeptides inhibit allospecific cytotoxic T lymphocyte recognition in an MHC-specific manner. J Immun 1986; 136: 6–11.PubMedGoogle Scholar
  21. 21.
    Muchmore A, Sathyamoorthy N, Decker J et al. Evidence that specific oligosaccharides block early events necessary for the expression of antigen-specific proliferation by human lymphocytes. J Immun 1980; 125: 1306–1311.PubMedGoogle Scholar
  22. 22.
    Jeske DJ, Capra JD. Immunoglobulins: Structure and Function. Paul W ed. Fundamental Immunology. New York: Raven Press 1984; 131.Google Scholar
  23. 23.
    Hickman S, Kulczycki A, Lynch R et al. Studies of the mechanism of tunicamycin inhibition of IgA and IgE secretion by plasma cells. J Biol Chem 1977; 252: 4402 4408.Google Scholar
  24. 24.
    Huff T, Uede T, Iwata M et al. Modulation of the biologic activities of IgE-binding factors III. Switching of a T-cell hybrid clone from the formation of IgE-suppressive factor to the formation of IgE-potentiating factor. J Immun 1983; 131: 1090–1095.PubMedGoogle Scholar
  25. 25.
    Huff T, Jardieu P, Ishizaka K. Regulatory effects of human IgE binding factors on the IgE response of rat lymphocytes. J Immun 1986; 136: 955–962.PubMedGoogle Scholar
  26. 26.
    Rademacher T, Parekh R, Dwek R. Glycobiology. Ann Rev Biochem 1988; 57: 792–794.CrossRefGoogle Scholar
  27. 27.
    Aoki N, Furukawa K, Iwatsuki K et al. A. bovine IgG heavy chain contains Nacetylgalactosaminylated N-linked sugar chains. Biochem Biophys Res Comm 1995; 210: 275–280.PubMedCrossRefGoogle Scholar
  28. 28.
    Ikeda K, Sannoh T, Kawasaki N et al. Serum lectin with known structure activates complement through the classical pathway. J Biol Chem 1987; 262: 7451–7454.PubMedGoogle Scholar
  29. 29.
    Reading PC, Hartley CA, Ezekowitz AB et al. A serum mannose-binding lectin mediates complement-dependent lysis of influenza virus-infected cells. Biochem Biophys Res Comm 1995; 217: 1128–1136.PubMedCrossRefGoogle Scholar
  30. 30.
    Lim B-L, Holmskov U. Expression of the carbohydrate recognition domain of bovine conglutinin and demonstration of its binding to iC3b and yeast mannan. Biochem Biophys Res Comm 1996; 218: 260–266.PubMedCrossRefGoogle Scholar
  31. 31.
    Vivier E, Sorrell J, Ackerly M et al. Developmental regulation of a mucin-like glycoprotein selectively expressed on natural killer cells. J Exp Med 1993; 178: 2023–2033.PubMedCrossRefGoogle Scholar
  32. 32.
    Ogata S, Maimonis PJ, Itzkowitz SH. Mucins bearing the cancer-associated sialosylTn antigen mediate inhibition of natural killer cell toxicity. Cancer Res 1992; 52: 4741–4746.PubMedGoogle Scholar
  33. 33.
    El Ouagari K, Teissié J, Benoist H. Glycophorin A protects K562 cells from natural killer cell attack. Role of oligosaccharides. J Biol Chem 1995; 270: 26970–26975.PubMedCrossRefGoogle Scholar
  34. 34.
    Bezouska K, Yuen CT, O’Brien J et al. Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. Nature 1994; 372: 150–157.PubMedCrossRefGoogle Scholar
  35. 35.
    Ahrens PB. Role of target cell glycoproteins in sensitivity to natural killer cell lysis. J Biol Chem 1993; 268: 385–391.PubMedGoogle Scholar
  36. 36.
    Voshol H, Dullens H, Otter W et al. Cell surface glycoconjugates as possible target structures for human natural killer cells: evidence against the involvement of glycolipids and N-linked carbohydrate chains. Glycobiology 1993; 3: 69–76.PubMedCrossRefGoogle Scholar
  37. 37.
    Mehta B, Collard H, Negrin R. The role of N-linked carbohydrate residues in lymphokine-activated killer cell-mediated cytolysis. Cell Immunol 1994; 155: 95–110.PubMedCrossRefGoogle Scholar
  38. 38.
    Arkwright P, Rademacher T, Boutignon F et al. Suppression of allogeneic reactivity in vitro by the syncytiotrophoblast membrane glycocalyx of the human term placenta is carbohydrate dependent. Glycobiology 1994; 4: 39–47.PubMedCrossRefGoogle Scholar
  39. 39.
    Kuhns W, Bramson S. Variable behavior of blood group H on HeLa cell population synchronized with thymidine. Nature 1968; 219: 938–939.PubMedCrossRefGoogle Scholar
  40. 40.
    Thomas D. Cyclic expression of blood group determinants in murine cells and their relationship to growth control. Nature 1971; 233: 317–321.PubMedCrossRefGoogle Scholar
  41. 41.
    Feizi T. Demonstration by monoclonal an tibodies that carbohydrate structures of glycoproteins and glycolipids are onto-developmental antigens. Nature 1985; 314: 1517.Google Scholar
  42. 42.
    Reid M. Associations of red blood cell membrane abnormalities with blood group phenotype. In: Garratty G. Immunobiology of Transfusion Medicine. New York: Marcel Dekker. 1994; 257–271.Google Scholar
  43. 43.
    Telen M. Erythrocyte blood group antigens: not so simple after all. Blood 1995; 85: 299–306.PubMedGoogle Scholar
  44. 44.
    Hakomori S. New directions in cancer therapy based on aberrant expression of glycosphingolipids:anti-adhesion and orthosignalling therapy. Cancer Cells 1991; 3: 461–470.PubMedGoogle Scholar
  45. 45.
    Moulds J. Association of blood group antigens with immunologically important proteins. In: Garratty G. Immunobiology of Transfusion Medicine. New York: Marcel Dekker 1994; 273–297.Google Scholar
  46. 46.
    King M. Blood group antigens on human erythrocytes-distribution, structure and possible functions. Biochim Biophys Acta 1994; 1197: 15–44.PubMedCrossRefGoogle Scholar
  47. 47.
    Ugorski B, Blackall D, Pâhlsson P et al. Recombinant Miltenberger I and II human blood group antigens:the role of glycosylation in cell surface expression and antigenicity of glycophorin A. Blood 1993; 82: 1913–1920.PubMedGoogle Scholar
  48. 48.
    Ridgwell K, Eyers S, Mawby W et al. Studies on the glycoprotein associated with Rh (Rhesus) blood group antigen expression in the human red blood cell membrane. J Biol Chem 1994; 269: 6410–6416.PubMedGoogle Scholar
  49. 49.
    Tanner M, Jenkins R, Anstee D et al. Abnormal carbohydrate composition of the major penetrating membrane protein of En(a-) human erythrocytes. Biochem J 1976; 155: 701–703.PubMedGoogle Scholar
  50. 50.
    Yang Z, Bergström J, Karlsson K. Glycoproteins with Gala4Gal are absent from human erythrocyte membranes, indicating that glycolipids are the sole carriers of blood group P activities. J Biol Chem 1994; 269: 14620–14624.PubMedGoogle Scholar
  51. 51.
    Karlsson K. Animal glycosphingolipids as membrane attachment sites for bacteria. Ann Rev Biochem 1989; 58: 309–350.PubMedCrossRefGoogle Scholar
  52. 52.
    Brown KE, Anderson SM, Young NS. Erythrocyte P antigen:cellular receptor for B19 parvovirus. Science 1993; 262: 114–117.PubMedCrossRefGoogle Scholar
  53. 53.
    Hardisty R. Disorders of platelets. II Functional abnormalities. In: Lilleyman J, Hann I, eds. Pediatric Hematology. Edinburgh: Churchill Livingstone, 1992; 167–199.Google Scholar
  54. 54.
    Phillips D, Charo I, Parise L et al. The platelet membrane glycoprotein IIb-IIIa complex. Blood 1988; 71: 831–843.PubMedGoogle Scholar
  55. 55.
    Da Silva M, Tamuri T, McBroom T et al. Tyrosine derivatization and preparative purification of the sialyl and asialyl N-linked oligosaccharides from porcine fibrinogen. Arch Biochem Biophys 1994; 312: 151–157.PubMedCrossRefGoogle Scholar
  56. 56.
    Gilman P. The role of the carbohydrate moiety in the biological properties of fibrinogen. J Biol Chem 1984; 259: 32483253.Google Scholar
  57. 57.
    Martinez J, Palascak JE, Kwasniak D. Abnormal sialic acid content of the dysfibrinogenemia associated with liver disease. J Clin Invest 1978; 61: 535–538.PubMedCrossRefGoogle Scholar
  58. 58.
    Beacham DA, Cruz MA, Handin RI. Glycoprotein Ib can mediate endothelial cell attachment to a von Willebrand factor substratum. Thromb Hemostasis 1995; 73: 309–317.Google Scholar
  59. 59.
    Clemetson K. Platelet activation:signal transduction via membrane receptors. Thromb Hemostas 1995; 74: 111–116.Google Scholar
  60. 60.
    Handin R, Wagner D. Molecular and cellular biology of von Willebrand factor. Prog Hemostasis Thromb 1989; 9: 233–259.Google Scholar
  61. 61.
    De Marco L, Mazzucato M, Masotti A et al. Localization and characterization of an a-thrombin binding site on platelet glycoprotein Iba. J Biol Chem 1994; 269: 64786484.Google Scholar
  62. 62.
    Gralnick H, Williams S, McKeown L et al. High-affinity a-thrombin binding to platelet glycoprotein Iba:identification of two binding domains. Proc Natl Acad Sci USA 1994; 91: 6334–6338.PubMedCrossRefGoogle Scholar
  63. 63.
    Korrel S, Clemetson K, van Halbeek H et al. Identification of a tetrasialylated monofucosylated tetra-antennary N-linked carbohydrate chain in human platelet glycocalicin. FEBS Lett 1988; 228: 321–326.PubMedCrossRefGoogle Scholar
  64. 64.
    Tsuji T, Tsunchisa S, Watanabe Y et al. The carbohydrate moiety of human platelet glycocalicin. J Biol Chem 1983; 258: 6335–6339.PubMedGoogle Scholar
  65. 65.
    Michelson A, Loscalzo J, Melnick B et al. Partial characterization of a binding site for von Willebrand factor on glycocalicin. Blood 1986; 67: 19–26.PubMedGoogle Scholar
  66. 66.
    Ruggeri Z. The platelet glycoprotein Ib-IX complex. Prog Hemostasis Thromb 1991; 10: 35–68.Google Scholar
  67. 67.
    Cruz M, Handin R, Wise R. The interaction of the von Willebrand factor-Al domain with platelet glycoprotein Ib/IX. J Biol Chem 1993; 268: 21238–21245.PubMedGoogle Scholar
  68. 68.
    Lynch D, Williams R, Zimmerman T et al. Biosynthesis of the subunits of factor VIIIR by bovine aortic endothelial cells. Proc Natl Acad Sci USA 1983; 80: 2738–2742.PubMedCrossRefGoogle Scholar
  69. 69.
    Tartakoff A. The combined function model of the Golgi complex:center for ordered processing of biosynthetic products of the rough ER. Int Rev Cytol 1983; 85: 221.PubMedCrossRefGoogle Scholar
  70. 70.
    Hironaka T, Furukawa K, Esmon P et al. Structural study of the sugar chains of porcine factor VIII- tissue and species specific glycosylation of Factor VIII. Arch Biochem Biophys 1993; 307: 316–330.PubMedCrossRefGoogle Scholar
  71. 71.
    Pirie-Sheperd S, Jett E, Andon N et al. Sialic acid content of plasminogen 2 glycoforms as a regulator of fibrinolytic activity. J Biol Chem 1995; 270: 5877–5881.CrossRefGoogle Scholar
  72. 72.
    Harris R, Leonard C, Guzzetta A et al. Tissue plasminogen activator has an O-linked fucose attached to threonine-61 in the epidermal growth factor domain. Biochemistry 1991; 30: 2311–2314.PubMedCrossRefGoogle Scholar
  73. 73.
    Hajjar K, Reynolds C. a-Fucose mediated binding and degradation of tissue type plasminogen activator by HepG2 cells. J Clin Invest 1994; 93: 703–710.PubMedCrossRefGoogle Scholar
  74. 74.
    Noorman F, Braat E, Rijken D. Degradation of tissue-type plasminogen activator by human monocyte derived macrophages is mediated by the mannose receptor and by the low density lipoprotein receptor-related protein. Blood 1995; 86: 3421–3427.PubMedGoogle Scholar
  75. 75.
    Björk I, Ylinenjärvi K, Olsen ST et al. Decreased affinity of recombinant antithrombin for heparin due to increased glycosylation. Biochem J 1992; 286: 793–800.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Inka Brockhausen
    • 1
  • William Kuhns
    • 1
  1. 1.Department of Biochemistry, Research Institute, Hospital for Sick ChildrenUniversity of TorontoTorontoCanada

Personalised recommendations