Invited Reviews
Role of Tissue Transglutaminase in Celiac Disease
Øyvind Molberg,
Stephen N. McAdam,
Ludvig M. Sollid,
Corresponding Author
Øyvind Molberg
Institute of Immunology, University of Oslo, RiksHospitalet, Oslo, Norway
Address correspondence and reprint requests to Dr. Øyvind Molberg, Institute of Immunology, Rikshospitalet, N-0027 Oslo, Norway.Search for more papers by this authorStephen N. McAdam
Institute of Immunology, University of Oslo, RiksHospitalet, Oslo, Norway
Search for more papers by this authorLudvig M. Sollid
Institute of Immunology, University of Oslo, RiksHospitalet, Oslo, Norway
Search for more papers by this authorØyvind Molberg,
Stephen N. McAdam,
Ludvig M. Sollid,
Corresponding Author
Øyvind Molberg
Institute of Immunology, University of Oslo, RiksHospitalet, Oslo, Norway
Address correspondence and reprint requests to Dr. Øyvind Molberg, Institute of Immunology, Rikshospitalet, N-0027 Oslo, Norway.Search for more papers by this authorStephen N. McAdam
Institute of Immunology, University of Oslo, RiksHospitalet, Oslo, Norway
Search for more papers by this authorLudvig M. Sollid
Institute of Immunology, University of Oslo, RiksHospitalet, Oslo, Norway
Search for more papers by this authorNo abstract is available for this article.
REFERENCES
- 1Sollid LM. Molecular basis of celiac disease. Ann Rev Immunol (in press).
- 2Marsh MN, Ensari A, Morgan S. Evidence that gluten sensitivity is an immunologic disease. Curr Opin Gastroenterol 1993; 9: 994–1000.
- 3Trier JS. Celiac sprue. N Engl J Med 1991; 325: 1709–19.
- 4Petronzelli F, Bonamico M, Ferrante P, et al. Genetic contribution of the HLA region to the familial clustering of coeliac disease. Ann Hum Genet 1997; 6: 307–17.
10.1046/j.1469-1809.1997.6140307.x Google Scholar
- 5Greco L, Corazza G, Babron MC, et al. Genome search in celiac disease. Am J Hum Genet 1998; 62: 669–75.
- 6Thorsby E. Invited anniversary review: HLA associated diseases. Hum Immunol 1997; 53: 1–11.
- 7Sollid LM, Thorsby E. HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis. Gastroenterology 1993; 105: 910–22.
- 8Lundin KEA, Scott H, Hansen T et al. Gliadin-specific, HLA-DQ(1*0501,1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med 1993; 178: 187–96.
- 9Lundin KEA, Scott H, Fausa O, Thorsby E, Sollid LM. T cells from the small intestinal mucosa of a DR4, DQ7/ DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8. Human Immunology 1994; 41: 285–91.
- 10Molberg Ø, Lundin KEA, Nilsen EM, et al. HLA restriction patterns of gliadin-and astrovirus-specific CD4+ T cells isolated in parallel from the small intestine of celiac disease patients. Tissue Antigens 1998; 52: 407–15.
- 11Troncone R, Gianfrani C, Mazzarella G, et al. Majority of gliadin-specific T-cell clones from celiac small intestinal mucosa produce interferon-and interleukin-4. Dig Dis Sci 1998; 43: 156–61.
- 12van de Wal Y, Kooy YC, van Veelen PA, et al. Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin. Proc Natl Acad Sci USA 1998; 95: 10050–4.
- 13Dieterich W, Ehnis T, Bauer M, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997; 3: 797–801.
- 14Dieterich W, Laag E, Schopper H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998; 115: 1317–21.
- 15Sulkanen S, Halttunen T, Laurila K, et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 1998; 115: 1322–8.
- 16Folk JE. Mechanism and basis for specificity of transglutaminase-catalyzed ε-γ-glutamyl) lysine bond formation. Adv Enzymol Relat Areas Mol Biol 1983; 54: 1–56.
- 17Lorand L, Conrad SM. Transglutaminases. Mol Cell Biochem 1984; 58: 9–35.
- 18Folk JE, Cole PW, Mullooly JP. Mechanism of action of guinea pig liver transglutaminase. V: The hydrolysis reaction. J Biol Chem 1968; 243: 418–27.
- 19Aeschlimann D, Paulsson M. Transglutaminases: Protein cross-linking enzymes in tissues and body fluids. Thromb Haemost 1994; 71: 402–15.
- 20Aeschlimann D, Paulsson M, Mann K. Identification of Gln726 in nidogen as the amine acceptor in transglutaminase-catalyzed cross-linking of laminin-nidogen complexes. J Biol Chem 1992; 267: 11316–21.
- 21Gorman JJ, Folk JE. Structural features of glutamine substrates for transglutaminases: Role of extended interactions in the specificity of human plasma factor XIIIa and of the guinea pig liver enzyme. J Biol Chem 1984; 259: 9007–10.
- 22Kahlem P, Terre C, Green H, Djian P. Peptides containing glutamine repeats as substrates for transglutaminase-catalyzed cross-linking: Relevance to diseases of the nervous system. Proc Natl Acad Sci USA 1996; 93: 14580–5.
- 23Greenberg CS, Birckbichler PJ, Rice RH. Transglutaminases: Multifunctional cross-linking enzymes that stabilize tissues. FASEB J 1991; 5: 3071–7.
- 24Jeong JM, Murthy SN, Radek JT, Lorand L. The fibronectin-binding domain of transglutaminase. J Biol Chem 1995; 10: 5654–8.
10.1074/jbc.270.10.5654 Google Scholar
- 25Nakaoka H, Perez DM, Baek KJ, et al. Gh: A GTP-binding protein with transglutaminase activity and receptor signaling function. Science 1994; 264: 1593–6.
- 26Aeschlimann D, Koeller MK, Allen-Hoffmann BL, Mosher DF. Isolation of a cDNA encoding a novel member of the transglutaminase gene family from human keratinocytes: Detection and identification of transglutaminase gene products based on reverse transcription-polymerase chain reaction with degenerate primers. J Biol Chem 1998; 273: 3452–60.
- 27Lu S, Saydak M, Gentile V, Stein JP, Davies PJ. Isolation and characterization of the human tissue transglutaminase gene promoter. J Biol Chem 1995; 270: 9748–56.
- 28Lu S, Davies PA. Regulation of the expression of the tissue transglutaminase gene by DNA methylation. Proc Natl Acad Sci USA 1997; 94: 4692–7.
- 29Kuncio GS, Tsyganskaya M, Zhu J, et al. TNF-α modulates expression of the tissue transglutaminase gene in liver cells. Am J Physiol 1998; 274: 1–5.
- 30Murthy SN, Velasco PT, Lorand L. Properties of purified lens transglutaminase and regulation of its transamidase/crosslinking activity by GTP. Exp Eye Res 1998; 67: 273–81.
- 31Suto N, Ikura K, Sasaki R. Expression induced by interleukin-6 of tissue-type transglutaminase in human hepatoblastoma HepG2 cells. J Biol Chem 1993; 268: 7469–73.
- 32Thomazy V, Fesus L. Differential expression of tissue transglutaminase in human cells: An immunohistochemical study. Cell Tissue Res 1989; 255: 215–24.
- 33Zhang J, Lesort M, Guttmann RP, Johnson GV. Modulation of the in situ activity of tissue transglutaminase by calcium and GTP. J Biol Chem 1998; 273: 2288–95.
- 34Lai TS, Bielawska A, Peoples KA, Hannun YA, Greenberg CS. Sphingosylphosphocholine reduces the calcium ion requirement for activating tissue transglutaminase. J Biol Chem 1997; 272: 16295–300.
- 35Aeschlimann D, Mosher D, Paulsson M. Tissue transglutaminase and factor XIII in cartilage and bone remodeling. Semin Thromb Hemost 1996; 22: 437–43.
- 36Schittny JC, Paulsson M, Vallan C, et al. Protein cross-linking mediated by tissue transglutaminase correlates with the maturation of extracellular matrices during lung development. Am J Respir Cell Mol Biol 1997; 17: 334–43.
- 37Wang JY, Johnson LR. Role of transglutaminase and protein cross-linking in the repair of mucosal stress erosions. Am J Physiol 1992; 262: 19–25.
- 38Amendola A, Gougeon ML, Poccia F, et al. Induction of “tissue” transglutaminase in HIV pathogenesis: Evidence for high rate of apoptosis of CD4+ T lymphocytes and accessory cells in lymphoid tissues. Proc Natl Acad Sci USA 1996; 93: 11057–62.
- 39Davies PJ, Davies DR, Levitzki A, et al. Transglutaminase is essential in receptor-mediated endocytosis of 2-macroglobulin and polypeptide hormones. Nature 1980; 283: 162–7.
- 40Davies PJ, Murtaugh MP. Transglutaminase and receptor-mediated endocytosis in macrophages and cultured fibroblasts. Mol Cell Biochem 1984; 58: 69–77.
- 41Teshigawara K, Kannagi R, Noro N, Masuda T. Possible involvement of transglutaminase in endocytosis and antigen presentation. Microbiol Immunol 1985; 29: 737–50.
- 42Pober JS, Strominger JL. Transglutaminase modifies the carboxy-terminal intracellular region of HLA-A and -B antigens. Nature 1981; 289: 819–21.
- 43Murtaugh MP, Arend WP, Davies PJ. Induction of tissue transglutaminase in human peripheral blood monocytes. J Exp Med 1984; 159: 114–25.
- 44Julian C, Speck NA, Pierce SK. Primary amines inhibit the triggering of B lymphocytes to antibody synthesis. J Immunol 1983; 130: 91–6.
- 45Metafora S, Peluso G, Ravagnan G, et al. Implication of transglutaminase in mitogen-induced human lymphocyte blast transformation. Adv Exp Med Biol 1988; 231–84.
- 46Leu RW, Herriott MJ, Moore PE, Orr GR, Birckbichler PJ. Enhanced transglutaminase activity associated with macrophage activation. Possible role in Fc-mediated phagocytosis. Exp Cell Res 1982; 141: 191–9.
- 47Murthy SN, Wilson JH, Lukas TJ, Kuret J, Lorand L. Cross-linking sites of the human tau protein, probed by reactions with human transglutaminase. J Neurochem 1998; 71: 2607–14.
- 48Selkoe DJ, Abraham C, Ihara Y. Brain transglutaminase: In vitro crosslinking of human neurofilament proteins into insoluble polymers. Proc Natl Acad Sci USA 1982; 79: 6070–4.
- 49Karpuj MV, Garren H, Slunt H, et al. Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington's disease brain nuclei. Proc Natl Acad Sci USA 1999; 46: 7388–93.
10.1073/pnas.96.13.7388 Google Scholar
- 50Kahlem P, Green H, Djian P. Transglutaminase action imitates Huntington's disease: Selective polymerization of Huntingtin containing expanded polyglutamine. Mol Cell 1998; 1: 595–601.
- 51Darro F, Cahen P, Vianna A, et al. Growth inhibition of human in vitro and mouse in vitro and in vivo mammary tumor models by retinoids in comparison with tamoxifen and the RU-486 anti-progestagen. Breast Cancer Res Treat 1998; 51: 39–55.
- 52Walker AM, Montgomery DW, Saraiya S, et al. Prolactin-immunoglobulin G complexes from human serum act as costimulatory ligands causing proliferation of malignant B lymphocytes. Proc Natl Acad Sci USA 1995; 92: 3278–82.
- 53D'Argenio G, Biancone L, Cosenza V, et al. Transglutaminases in Crohn's disease. Gut 1995; 37: 690–5.
- 54Piacentini M, Colizzi V. Tissue transglutaminase: Apoptosis versus autoimmunity. Immunol Today 1999; 20: 130–4.
- 55Utz PJ, Anderson P. Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens. Arthritis Rheum 1998; 41: 1152–60.
- 56Hanson SR, Smith DL, Smith JB. Deamidation and disulfide bonding in human lens-crystallins. Exp Eye Res 1998; 67: 301–12.
- 57Lampi KJ, Ma Z, Hanson SR, et al. Age-related changes in human lens crystallins identified by two-dimensional electrophoresis and mass spectrometry. Exp Eye Res 1998; 67: 31–43.
- 58Schmidt G, Selzer J, Lerm M, Aktories K. The rho-deamidating cytotoxic necrotizing factor 1 from escherichia coli possesses transglutaminase activity: Cysteine 866 and histidine 881 are essential for enzyme activity. J Biol Chem 1998; 273: 13669–74.
- 59Bruce SE, Bjarnason I, Peters TJ. Human jejunal transglutaminase: Demonstration of activity, enzyme kinetics and substrate specificity with special relation to gliadin and coeliac disease. Clin Sci (Colch) 1985; 68: 573–9.
- 60D'Argenio G, Sorrentini I, Ciacci C, et al. Human serum transglutaminase and coeliac disease: Correlation between serum and mucosal activity in an experimental model of rat small bowel enteropathy. Gut 1989; 30: 950–4.
- 61Larre C, Chiarello M, Blanloeil Y, Chenu M, Gueguen J. Gliadin modifications catalysed by guinea pig liver transglutaminase. J Food Biochem 1993; 112: 267–82.
10.1111/j.1745-4514.1993.tb00472.x Google Scholar
- 62Dietrich W, Ehnis T, Bauer M, Riecken EO, Schuppan D. Gliadin is a preferred substrate for tissue transglutaminase, the autoantigen in coeliac disease (abstract). Gastroenterology 1997; A359.
- 63Sollid LM, Molberg Ø, McAdam S, Lundin KEA. Autoantibodies in coeliac disease: Tissue transglutaminase—guilt by association. Gut 1997; 41: 851–2.
- 64Paul WE, Katz DH, Goidl EA, Benacerraf B. Carrier function in anti-hapten immune responses. II: Specific properties of carrier cells capable of enhancing anti-hapten antibody responses. J Exp Med 1970; 132: 283–99.
- 65Picarelli A, Maiuri L, Frate A, et al. Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Lancet 1996; 348: 1065–7.
- 66Vogelsang H, Schwarzenhofer M, Granditsch G, Oberhuber G. In vitro production of endomysial antibodies in cultured duodenal mucosa from patients with celiac disease. Am J Gastroenterol 1999; 94: 1057–61.
- 67Molberg Ø, Mcadam SN, Körner R, et al. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 1998; 4: 713–7.
- 68Sjöström H, Lundin KEA, Molberg Ø, et al. Identification of a gliadin T-cell epitope in coeliac disease: General importance of gliadin deamidation for intestinal T-cell recognition. Scand J Immunol 1998; 48: 111–5.
- 69van de Wal Y, Kooy Y, van Veelen P, et al. Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J Immunol 1998; 161: 1585–8.
- 70Arentz-Hansen EH, Körner R, Molberg Ø, et al. The intestinal T cell response to -gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med (in press).
- 71Quarsten H, Molberg Ø, Fugger L, Mcadam SN, Sollid LM. HLA binding and T cell recognition of a tissue transglutaminase-modified gliadin epitope. Eur J Immunol 1999; 99: 2506–14.
10.1002/(SICI)1521-4141(199908)29:08<2506::AID-IMMU2506>3.0.CO;2-9 Google Scholar
- 72Kwok WW, Domeier ME, Johnson ML, Nepom GT, Koelle DM. HLA-DQB1 codon 57 is critical for peptide binding and recognition. J Exp Med 1996; 183: 1253–8.
- 73Johansen BH, Vartdal F, Eriksen JA, Thorsby E, Sollid LM. Identification of a putative motif for binding of peptides to HLA-DQ2. Int Immunol 1996; 79: 177–82.
10.1093/intimm/8.2.177 Google Scholar
- 74Vartdal F, Johansen BH, Friede T, et al. The peptide binding motif of the disease associated HLA-DQ (1* 0501, 1* 0201) molecule. Eur J Immunol 1996; 26: 2764–72.
- 75van de Wal Y, Kooy YC, Drijfhout JW, Amons R, Koning F. Peptide binding characteristics of the coeliac disease-associated DQ(1*0501, 1*0201) molecule. Immunogenetics 1996; 44: 246–53.
- 76Gjertsen HA, Sollid LM, Ek J, Thorsby E, Lundin KE. T cells from the peripheral blood of coeliac disease patients recognize gluten antigens when presented by HLA-DR, -DQ, or -DP molecules. Scand J Immunol 1994; 39: 567–74.
- 77Tabor CW, Tabor H. Polyamines. Annu Rev Biochem 1984; 53: 749–90.
- 78Nunes I, Gleizes PE, Metz CN, Rifkin DB. Latent transforming growth factor-beta binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-β. J Cell Biol 1997; 136: 1151–63.
- 79Letterio JJ, Roberts AB. Regulation of immune responses by TGF-β. Annu Rev Immunol 1998; 16: 137–61.
- 80Feng JF, Readon M, Yadav SP, Im MJ. Calreticulin down-regulates both GTP binding and transglutaminase activities of transglutaminase II. Biochemistry 1999; 38: 10743–9.
- 81Krupickova S, Tuckova L, Flegelova Z, et al. Identification of common epitopes on gliadin, enterocytes, and calreticulin recognised by antigliadin antibodies of patients with coeliac disease. Gut 1999; 44: 168–73.
- 82Nikoshkov A, Falorni A, Lajic S, et al. A conformation-dependent epitope in Addison's disease and other endocrinological autoimmune diseases maps to a carboxyl-terminal functional domain of human steroid 21-hydroxylase. J Immunol 1999; 162: 2422–6.
- 83Kohno Y, Yamaguchi F, Saito K, et al. Anti-thyroid peroxidase antibodies in sera from healthy subjects and from patients with chronic thyroiditis: Differences in the ability to inhibit thyroid peroxidase activities. Clin Exp Immunol 1991; 85: 459–63.
- 84Schwartz HL, Chandonia JM, Kash SF, et al. High-resolution autoreactive epitope mapping and structural modeling of the 65 kDa form of human glutamic acid decarboxylase. J Mol Biol 1999; 287: 983–99.
- 85Sollid LM, Scott H. New tool to predict celiac disease on its way to the clinics. Gastroenterology 1998; 115: 1584–6.
- 86Halttunen T, Maki M. Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. Gastroenterology 1999; 116: 566–72.
- 87Dieterich W, Laag E, Bruckner-Tuderman L, et al. Antibodies to tissue transglutaminase as serologic markers in patients with dermatitis herpetiformis. J Invest Dermatol 1999; 113: 133–6.
- 88Meadows L, Wang W, Den HJ, et al. The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition. Immunity 1997; 6: 273–81.
- 89Skipper JC, Hendrickson RC, Gulden PH, et al. An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins. J Exp Med 1996; 183: 527–34.
- 90Selby M, Erickson A, Dong C, et al. Hepatitis C virus envelope glycoprotein E1 originates in the endoplasmic reticulum and requires cytoplasmic processing for presentation by class I MHC molecules. J Immunol 1999; 162: 669–76.
- 91Mamula MJ, Gee RJ, Elliott JI, et al. Isoaspartyl post-translational modification triggers autoimmune responses to self-proteins. J Biol Chem 1999; 274: 22321–7.
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