Toxic, immunostimulatory and antagonist gluten peptides in Celiac disease

Current Medicinal Chemistry

Volumn 16, Issue 12, 2009, Pages 1489-1498

  Silano, Marco ^a   Vincentini, Olimpia ^a   de Vincenzi, Massimo ^a  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

Author keywords

Celiac disease; DQ binding; Gluten; Mucosal inflammation; T cells epitopes; Tissue transglutaminase

Indexed keywords

ALCOHOL; ALTERED PEPTIDE LIGAND; AMINO ACID; GLIADIN; GLUTEN; HLA DQ2 ANTIGEN; HLA DQ8 ANTIGEN; HORDEIN; PEPTIDE DERIVATIVE; PROTEIN; SECALIN; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; AMINO ACID SEQUENCE; ANTIGEN EXPRESSION; ANTIGEN PRESENTING CELL; AUTOIMMUNE DISEASE; BARLEY; CELIAC DISEASE; CELL SURFACE; CEREAL; ENTEROPATHY; GLUTEN FREE DIET; HAPLOTYPE; HISTOPATHOLOGY; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOSTIMULATION; INFLAMMATION; INNATE IMMUNITY; INTESTINE CRYPT; INTESTINE MUCOSA; INTESTINE VILLUS ATROPHY; LAMINA PROPRIA; LYMPHOCYTIC INFILTRATION; PATHOGENESIS; PROTEIN BINDING; PROTEIN STRUCTURE; REVIEW; RYE; T LYMPHOCYTE; WHEAT;

ADJUVANTS, IMMUNOLOGIC; AMINO ACID SEQUENCE; CELIAC DISEASE; GLUTENS; HUMANS; INTESTINAL MUCOSA; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; PEPTIDES;

EID: 65649151999     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986709787909613     Document Type: Review

References (97)

1. Fasano, A.; Catassi, C. Current approaches to diagnosis and treatment of celiac disease: An evolving spectrum. Gastroenterology, 2001, 120, 636-51.
2. Kagnoff, M.E. Overview and pathogenesis of celiac disease. Gastroenterology, 2005, 128, S10-18.
3. Shewry, P.R.; Tatham, A.S.; Kasarda D.D. Celiac disease Blackwell Scientific Publication; London, 1992.
4. Alaedini, A.; Green, P.H.R. Narrative review: Celiac disease: understanding a complex autoimmune disorder. Ann. Intern. Med., 2005, 142, 289-98.
5. Green, P.H.R.; Jabri, B. Coeliac disease. Lancet, 2003, 362, 383.
6. Rostom, A.; Dubé, C.; Cranney, A.; Saloojee, N.; Sy, R.; Garritty, C.; Sampson, M.; Zhang, L.; Yazdi, F., Mamaladze, V.; Pan, I.; MacNeil, J.; Mack, D.; Patel, D.; Moher, D. The diagnostic accuracy of serological test for celiac disease: A systematic review. Gastroenterology, 2005, 128, S38-46
7. Hopper, A.D.; Cross, S.S.; Sanders, D.S. Patchy villous atrophy in adult patients with suspect gluten intolerance: Is a multiple duodenal biopsy strategy appropriate? Endoscopy, 2008, 40, 219-24.
8. Bonamico, M.; Mariani, P.; Thanasi, E.; Ferri, M.; Nenna, R.; Tiberti, C.; Mora, B.; Mazzilli, M.C.; Magliocca, F.M. Patchy villous atrophy of the duodenum in childhood celiac disease. J. Pediatr. Gastroenterol. Nutr., 2004, 38, 204-7.
9. Green, P.H.; Cellier, C. Celiac disease. N. Engl. J. Med., 2007, 357, 1731-43.
10. Catassi, C.; Bearzi, I.; Holmes, G.K. Association of celiac disease and intestinal lymphomas and other cancers. Gastroenterology, 2005, 128, S79-86.
11. Silano, M.; Volta, U.; De Vincenzi, A.; Dessi, M.; De Vincenzi, M. Collaborating centers of the italian registry of the complications of coeliac disease: Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig. Dis. Sci., 2008, 53, 972-6.
12. Jabri, B.; Kasarda, D.D.; Green, P.H.R. Innate and adaptive immunity: the yin and yiang of celiac disease. Immun. Rev., 2005, 206, 219-31.
13. Ciclitira, P.J.; Evans, D.J.; Fagg, N.L.; Lennox, E.S.; Dowling, R.H. Clinical testing of gliadin fractions in celiac disease. Clin. Sci. (Lond)., 1984, 66, 357-64.
14. Sollid, L.M. Celiac disease: Dissecting a complex inflammatory disease. Nat. Rev. Immunol., 2002, 2, 647-55.
15. Kilmartin, C.; Wieser, H.; Abuzakouk M.; Kelly, J.; Jackson, J.; Feighery, C. Intestinal T cell responses to cereal proteins in celiac disease. Dig. Dis. Sci., 2006, 51, 202-9.
16. McGough, N.; Cummings, J.H. Coelic disease: A diverse clinical syndrome caused by intolerance of wheat, barley and rye. Proc. Nutr. Soc., 2005, 64, 434-50.
17. Ciclitira, P.J.; Ellis, H.J.; Lundin, K.E. Gluten-free - what is toxic? Best Pract. Res. Clin. Gastroenterol., 2005, 19, 359-71.
18. Sadiq Butt, M.; Tahir-Nadeem, M.; Khan, M.K.; Shabir, R.; Butt, M.S. Oat unique among the cereals. Eur. J. Nutr., 2008, 47, 68-79.
19. Holm, K.; Mäki, M.; Vuolteenaho, N.; Mustalahti, K.; Ashorn, M.; Ruuska, T.; Kaukinen, K. Oats in the treatment of childhood coeliac disease: A 2-year controlled trial and a long-term clinical follow-up study. Aliment Pharmacol. Ther., 2006, 23, 1463-72.
20. Kupper C. Dietary guidelines and implementation for celiac disease. Gastroenterology, 2005, 128, S121-7.
21. Wolters, V.M.; Wijmenga, C. Genetic background of celiac disease and its implications. Am. J. Gastroenterol., 2008, 103, 190.
22. van Heel, D.A.; Hunt, K.; Greco, L.; Wijmenga, C. Genetics in celiac disease. Best Pract. Res. Clin. Gastroenterol., 2005, 19, 323-39.
23. Vader, W.; Stepniak, D.; Kooy, Y.; Mearin, L.; Thompson, A.; van Rood, J.J.; Spaenij, L.; Koning, F. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. PNAS, 2003, 100, 12390-5.
24. Sollid, L.M.; Markussen, G.; Ek, J.; Gjerde. H.; Vartdal, F.; Thorsby, E. Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J. Exp. Med., 1989, 169, 345-50.
25. Hunt, K.A.; Zhernakova, A.; Turner, G.; Heap G.A.; Franke, L.; Bruinenberg, M.; Romanos, J.; Dinesen, L.C.; Ryan, A.W.; Panesar, D.; Gwilliam, R.; Takeuchi, F.; McLaren, W.M.; Holmes G.K.; Howdle, P.D.; Walters, JR.; Sanders, DS.; Playford, R.J.; Trynka G.; Mulder C.J.; Mearin, M.L.; Verbeek, W.H.; Trimble, V.; Stevens F.M.; O'Morain C.; Kennedy N.P.; Kelleher, D.; Pennington D,J.; Strachan, D.P.; McArdle, W.L.; Mein, C.A.; Wapenaar, M.C.; Deloukas, P.; McGinnis, R.; McManus, R.; Wijmenga, C.; van Heel, DA. Newly identified genetic risk variants for celiac disease related to the immune response. Nat. Genet., 2008, 40, 395-402.
26. Greco, L.; Corazza, G.; Babron MC.; Clot, F.; Fulchignoni-Lataud, M.C.; Percolo, S.; Zavattari, P.; Bouguerra, F.; Dib, C.; Tosi, R.; Troncone, R.; Ventura, A.; Mantavoni, W.; Magazzù, G.; Gatti, R.; Lazzari, R.; Giunta, A.; Perri, F.; Iacono, G.; Cardi, E.; de Virgiliis, S.; Cataldo, F.; De Angelis, G.; Musumeci, S. Clerget-Darpoux, F.: Existence of a genetic risk factor on chromosome 5q in Italian coeliac disease families. Am. J. Hum. Genet., 1998, 62, 669.
27. Diosdado, B.; Wijmenga, C. Molecular mechanisms of the adaptive, innate and regulatory immune responses in the intestinal mucosa of celiac disease patients. Expert Rev. Mol., 2005, 5, 681-700.
28. Kagnoff, M.F. Celiac disease: Pathogenesis of a model immunogenetic disease. J. Clin. Invest., 2007, 117, 41-9.
29. Esposito, C.; Caputo, I.; Troncone, R. New therapeutic strategy for coeliac disease: Tissue transglutaminase as a target. Curr. Med. Chem., 2007, 14, 2572.-80.
30. Dieterich, W.; Ehnis, T.; Bauer, M.; Donner, P.; Volta, U.; Riecken, E.O.; Schuppan, D. Identification of tissue transglutaminase as the antigen of celiac disease. Nat. Med., 1997, 3, 797-801.
31. Molberg, O.; Mcadam, S.N.; Körner, R.; Quarsten, H.; Kristiansen, C.; Madsen, L.; Fugger, L.; Scott, H.; Norén, O.; Roepstorff, P.; Lundin, K.E.; Sjöström, H.; Sollid, L.M. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat. Med., 1998, 4, 713-7.
32. van de Wal, Y.; Kooy, Y.; van Veelen, P.; Peña, S.; Mearin, L.; Papadopoulos, G.; Koning F. Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J. Immunol., 1998, 161, 1585-8.
33. Vader, L.W.; de Ru, A.; van der Wal, Y.; Kooy, Y.M.C.; Benckhuijsen, W.; Mearin, M.L.; Drijfhout, J.W.; van Veelen, P.; Koning, F. Specificity of tissue transglutaminase explains cereal toxicity in celiac disease. J. Exp. Med., 2002, 195, 643-9.
34. Kagnoff, M.; Paterson, Y.; Kumar, P.; Kasarda, D.; Carbone, F.; Unsworth, D.; Austin, R. Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease. Gut, 1987, 28, 995-1001.
35. Zanoni, G.; Navone, R.; Lunardi, C.; Tridente, G.; Bason, C.; Sivori, S.; Beri, R.; Dolcino, M.; Valletta, E.; Corrocher, R.; Puccetti, A. In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes. PLoS Med., 2006, 3, e358.
36. Di Pierro, M.; Lu, R.; Uzzau, S.; Wang, W.; Margaretten, K.; Pazzani, C.; Maimone, F.; Fasano, A. Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. J. Biol. Chem., 2001, 276, 19160-5.
37. Schumann, M.; Richter, J.; Wedell, I.; Moos, V.; Zimmermann-Kordmann, M.; Schneider, T.; Daum, S.; Zeitz, M.; Fromm, M.; Schulzke, J. Mechanism of epithelial translocation of the alpha(2)-gliadin-33mer in coeliac sprue. Gut, 2008, 57, 747-54.
38. Matysiak-Budnik, T.; Moura, I.; Arcos-Fajardo, M.; Lebreton, C.; Ménard, S.; Candalh, C.; Ben-Khalifa, K.; Dugave, C.; Tamouza, H.; van Niel, G.; Bouhnik, Y.; Lamarque, D.; Chaussade, S.; Malamut, G.; Cellier, C.; Cerf-Bensussan, N.; Monteiro, R.; Heyman, M. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J. Exp. Med., 2008, 205, 143-54.
39. Nilsen, E.; Jahnsen, F.; Lundin, K.; Johansen, F.; Fausa, O.; Sollid, L.; Jahnsen, J.; Scott, H.; Brandtzaeg, P. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology, 1998, 115, 551-63.
40. Przemioslo, R.; Lundin, K.; Sollid, L.; Nelufer, J.; Ciclitira, P. Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody. Gut, 1995, 36, 874-9.
41. Monteleone, G.; Monteleone, I.; Fina, D.; Vavassori, P.; Del Vecchio Blanco, G.; Caruso, R.; Tersigni, R.; Alessandroni, L.; Biancone, L.; Naccari, G.; MacDonald, T.; Pallone, F. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Gastroenterology, 2005, 128, 687-94.
42. Monteleone, I.; Monteleone, G.; Del Vecchio Blanco, G.; Vavassori, P.; Cucchiara, S.; MacDonald, T.; Pallone, F. Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa. Gut, 2004, 53, 1090.
43. Gianfrani, C.; Levings, M.; Sartirana, C.; Mazzarella, G.; Barba, G.; Zanzi, D.; Camarca, A.; Iaquinto, G.; Giardullo, N.; Auricchio, S.; Troncone, R.; Roncarolo, M. Gliadin-specific type 1 regulatory T cells from the intestinal mucosa of treated celiac patients inhibit pathogenic T cells. J. Immunol., 2006, 177, 4178-86.
44. Salvati, V.; Mazzarella, G.; Gianfrani, C.; Levings, M.; Stefanile, R.; De Giulio, B.; Iaquinto, G.; Giardullo, N.; Auricchio, S.; Roncarolo, M.; Troncone, R. Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa. Gut, 2005, 54, 46-53.
45. Koning, F. Celiac disease: Caught between a rock and a hard place. Gastroenterology, 2005, 129, 1294-301.
46. Stepniak, D.; Koning, F. Celiac disease - sandwiched between innate and adaptive immunità. Hum. Immunol., 2006, 67, 460-8.
47. Maiuri, L.; Ciacci, C.; Auricchio, S.; Brown, V.; Quaratino, S.; Londei, M. IL-15 mediates epithelial changes in celiac disease. Gastroenterology, 2000, 119, 996-1006.
48. Mazzarella, G.; MacDonald, T.; Salvati, V.; Mulligan, P.; Pasquale, L.; Stefanile, R.; Lionetti, P.; Auricchio, S.; Pallone, F.; Troncone, R.; Monteleone, G. Constitutive activation of the signal transducer and activator of transcription pathway in celiac disease lesions. Am. J. Pathol., 2003, 162, 1845-55.
49. Maiuri, L.; Ciacci, C.; Raia, V.; Vacca, L.; Ricciardelli, I.; Raimondi, F.; Auricchio, S.; Quaratino, S.; Londei, M. FAS engagement drives apoptosis of enterocytes of coeliac patients. Gut, 2001, 48, 418-24.
50. Maiuri, L.; Picarelli, A.; Boirivant, M.; Coletta, S.; Mazzilli, M.; De Vincenzi, M.; Londei, M.; Auricchio, S. Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients. Gastroenterology, 1996, 110, 1368-78.
51. Di Sabatino, A.; Pickard, K.; Gordon, J.; Salvati, V.; Mazzarella, G.; Beattie, R.; Vossenkaemper, A.; Rovedatti, L.; Leakey, N.; Croft, N.; Troncone, R.; Corazza, G.; Stagg, A.; Monteleone, G.; MacDonald, T.T. Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. Gastroenterology, 2007, 133, 1175-87.
52. De Vincenzi, M.; Stammati, A.; Luchetti, R.; Silano, M.; Gasbarrini, G.; Silano, V. Structural specificities and significance for coeliac disease of wheat gliadin peptides able to agglutinate or to prevent agglutination of K562(S) cells. Toxicology, 1998, 127, 97-106.
53. Cornell, H.J.; Auricchio, S.; De Ritis, G.; De Vincenzi, M.; Maturi, L.; Raia, V.; Silano, V. Intestinal mucosa of celiacs in remission is unable to abolish toxicity of gliadin peptides on in vitro developing fetal rat intestine and cultured atrophic celiac mucosa. Pediatr. Res., 1988, 24, 233-7.
54. Giovannini, C.; Sanchez, M.; Straface, E.; Scazzocchio, B.; Silano, M.; De Vincenzi, M. Induction of apoptosis in caco-2 cells by wheat gliadin peptides. Toxicology, 2000, 145, 63-71.
55. Maiuri, L.; Ciacci, C.; Ricciardelli, I.; Vacca, L.; Raia, V.; Rispo, A.; Griffin, M.; Issekutz, T.; Quaratino, S.; Londei, M. Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology, 2005, 129, 1400-13.
56. Gianfrani, C.; Auricchio, S.; Troncone, R. Adaptive and innate immune response in celiac disease. Immunol. Lett., 2005, 99, 141-5.
57. de Ritis, G.; Auricchio, S.; Jones, H.; Lew, E.; Bernardin, J.; Kasarda, D. In vitro (organ culture) sudies of the toxicity of specific A-gliadin peptides in celiac disease. Gastroenterology, 1988, 94, 41-9.
58. Maiuri, L.; Troncone, R.; Mayer, M.; Coletta, S.; Picarelli, A.; De Vincenzi, M.; Pavone, V.; Auricchio, S. In vitro activities of Agliadin- related synthetic peptides: Damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa. Scand. J. Gastroenterol., 1996, 31, 247-53.
59. Ciclitira, P.J.; Ellis, H.J. In vivo gluten ingestion in celiac disease. Dig. Dis., 1998, 16, 337-40.
60. Lähteenoja, H.; Mäki, M.; Viander, M.; Toivanen, A.; Syrjanen, S. Local challenge of oral mucosa with gliadin in patients with coeliac disease. Clin. Exp. Immunol., 2000, 120, 38-45.
61. Johansen, B.; Gjertsen, H.; Vartdal, F.; Buus, S.; Thorsby, E.; Lundin, K.; Sollid, L. Binding of peptides from the N-terminal region of alpha-gliadin to the celiac disease-associated HLA-DQ2 molecule assessed in biochemical and T cell assays. Clin. Immunol. Immunopathol., 1996, 79, 288-93.
62. Maiuri, L.; Ciacci, C.; Ricciardelli, I.; Vacca, L.; Raia, V.; Auricchio, S.; Picard, J.; Osman, M.; Quaratino, S.; Londei, M. Association between innate response to gliadin and activation of pathogenetic T cells in coeliac disease. Lancet, 2003, 362, 30-7.
63. Barone, M.; Gimigliano, A.; Castoria, G.; Paolella, G.; Maurano, F.; Paparo, F.; Maglio, M.; Mineo, A.; Miele, E.; Nanayakkara, M.; Troncone, R.; Auricchio, S. Growth factor-like activity of gliadin, an alimentary protein: Implications for coeliac disease. Gut, 2007, 56, 480-8.
64. Anderson, R.; Degano, P.; Godkin, A.; Jewell, D.; Hill, A. In vivo antigen challenge in celiac disease identifies a single transglutaminase- modified peptide as the dominant A-gliadin T-cell epitope. Nat. Med., 2000, 6, 337-42.
65. Arentz-Hansen, H.; Körner, R.; Molberg, O.; Quarsten, H.; Vader, W.; Kooy, Y.; Lundin, K.; Koning, F.; Roepstorff, P.; Sollid, L.; McAdam, S. The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J. Exp. Med., 2000, 191, 603-12.
66. Fraser, J.; Engel, W.; Ellis, H.; Moodie, S.; Pollock, E.; Wieser, H.; Ciclitira, P. Coelic disease: in vivo toxicity of the putative immunodominant epitope. Gut, 2003, 52, 1698-702.
67. Shan, L.; Molberg, Ø.; Parrot, I.; Hausch, F.; Filiz, F.; Gray, G.; Sollid, L.; Khosla, C. Structural basis for gluten intolerance in celiac sprue. Science, 2002, 297, 2275-9.
68. Kim, C.; Quarsten, H.; Bergseng, E.; Khosla, C.; Sollid, L. Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease. Proc. Natl. Acad. Sci. USA, 2004, 101, 4175-9.
69. Henderson, K.; Reid, H.; Borg, N.; Broughton, S.; Huyton, T.; Anderson, R.; McCluskey, J.; Rossjohn, J. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 2007, 63, 1021-5.
70. Costantini, S.; Rossi, M.; Colonna, G.; Facchiano, A. Modelling of HLA-DQ2 and its interaction with gluten peptides to explain molecular recognition in celiac disease. J. Mol. Graph Model., 2005, 23, 419-31.
71. Qiao, S.; Bergseng, E.; Molberg, O.; Jung, G.; Fleckenstein, B.; Sollid, L. Refining the rules of gliadin T cell epitope binding to the disease-associated DQ2 molecule in celiac disease: Importance of proline spacing and glutamine deamidation. J. Immunol., 2005, 175, 254-61.
72. Bergseng, E.; Sidney, J.; Sette, A.; Sollid, L. Analysis of the binding of gluten T-cell epitopes to various human leukocytes antigen class II molecules. Hum. Immunol., 2008, 69, 94-100.
73. Stepniak, D.; Vader, L.; Kooy, Y.; van Veelen, P.; Moustakas, A.; Papandreou, N.; Eliopoulos, E.; Drijfhout, J.; Papadopoulos, G.; Koning, F. T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by a N-terminal proline at p-1. Immunogenetics, 2005, 57, 8-15.
74. Stepniak, D.; Wiesner, M.; de Ru, A.; Moustakas, A.; Drijfhout, J.; Papadopoulos, G.; van Veelen, P.; Koning, F. Large-scale characterization of natural ligands explains the unique gluten-binding properties of HLA-DQ2. J. Immunol., 2008, 180, 3268-78.
75. Mazzarella, G.; Stefanile, R.; Camarca, A.; Giliberti, P.; Cosentini, E.; Marano, C.; Iaquinto, G.; Giardullo, N.; Auricchio, S.; Sette, A.; Troncone, R.; Gianfrani, C. Gliadin activates HLA class Irestricted CD8+ T cells in celiac disease intestinal mucosa and induces the enterocyte apoptosis. Gastroenterology, 2008, 134, 1017-27.
76. van de Wal, Y.; Kooy, Y.; van Veelen, P.; Peña, S.; Mearin, L.; Molberg, O.; Lundin, K.; Sollid, L.; Mutis, T.; Benckhuijsen, W.; Drijfhout, J.; Koning, F. Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin. Proc. Natl. Acad. Sci. USA, 1998, 95, 10050-4.
77. Henderson, K.; Tye-Din, J.; Reid, H.; Chen, Z.; Borg, N.; Beissbarth, T.; Tatham, A.; Mannering, S.; Purcell, A.; Dudek, N.; van Heel, D.; McCluskey, J.; Rossjohn, J.; Anderson, R. A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease. Immunity, 2007, 27, 23-34.
78. Tollefsen, S.; Arentz-Hansen, H.; Fleckenstein, B.; Molberg, O.; Ráki, M.; Kwok, W.; Jung, G.; Lundin, K.; Sollid, L. HLA-DQ2 and - DQ8 signatures of gluten T cell epitopes in celiac disease. J. Clin. Invest., 2006, 116, 2226-36.
79. Mazzarella, G.; Maglio, M.; Paparo, F.; Nardone, G.; Stefanile, R.; Greco, L.; van de Wal, Y.; Kooy, Y.; Koning, F.; Auricchio, S.; Troncone, R. An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients. Gut, 2003, 52, 57-62.
80. Molberg, Ø.; Solheim Flaete, N.; Jensen, T.; Lundin, K.; ArentzHansen, H.; Anderson, O.; Kjersti Uhlen, A.; Sollid, L. Intestinal T-cell response to high-molecular-weight glutenins in celiac disease. Gastroenterology, 2003, 125, 337-44.
81. Vader, W.; Kooy, Y.; Van Veelen, P.; De Ru, A.; Harris, D.; Benckhuijsen, W.; Peña, S.; Mearin, L.; Drijfhout, J.; Koning, F. The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology, 2002, 122, 1729-37.
82. Spaenij-Dekking, L.; Kooy-Winkelaar, Y.; van Veelen, P.; Drijfhout, J.; Jonker, H.; van Soest, L.; Smulders, M.; Bosch, D.; Gilissen, L.; Koning, F. Natural variation in toxicity of wheat:pOtential for selection of nontoxic varieties for celiac disease Gastroenterology, 2005, 129, 797-806.
83. Molberg, O.; Uhlen, A.; Jensen, T.; Flaete, N.; Fleckenstein, B.; Arentz-Hansen, H.; Raki, M.; Lundin, K.; Sollid, L. mapping of gluten T-cell epitopes in the bread wheat ancestors: Implications for celiac disease. Gastroenterology, 2005, 128, 393-401.
84. Vader, L.; Stepniak, D.; Bunnik, E.; Kooy, Y.; de Haan, W.; Drijfhout, J.; Van Veelen, P.; Koning, F. Characterization of cereal toxicity for celiac disease patients based on protein homology in grains. Gastroenterology, 2003, 125, 1105-13.
85. Arentz-Hansen, H.; Fleckenstein, B.; Molberg, Ø.; Scott, H.; Koning, F.; Jung, G.; Roepstorff, P.; Lundin, K.; Sollid, L. The molecular basis for oat intolerance in patients with celiac disease. PLoS Med., 2004, 1, e1.
86. Silano, M.; Di Benedetto, R.; Maialetti, F.; De Vincenzi, A.; Calcaterra, R.; Cornell, H.; De Vincenzi, M. Avenins from different cultivars of oats elicit response by coeliac peripheral lymphocytes. Scand. J. Gastroenterol., 2007, 42, 1302-5.
87. Holm, K.; Mäki, M.; Vuolteenaho, N.; Mustalahti, K.; Ashorn, M.; Ruuska, T.; Kaukinen, K. Oats in the treatment of childhood celiac disease: A 2-years controlled trials and a long-term clinical follow-up study. Aliment Pharmacol. Ther., 2006, 23, 1463-72.
88. Biagi, F.; Ellis, H.; Parnell, N.; Shidrawi, R.; Thomas, P.; O'Reilly, N.; Corazza, G.; Ciclitira, P. A non toxic analogue of a coeliac-activating gliadin peptide: A basis for immunomodulation? Aliment Pharmacol. Ther., 1999, 13, 945-50.
89. Ellis, H.; Pollock, E.; Engel, W.; Fraser, J.; Rosen-Bronson, S.; Wieser, H.; Ciclitira, P. Investigation of the putative immunodominant T cell epitopes in coeliac disease. Gut, 2003, 52, 212-7.
90. Anderson, R.; van Heel, D.; Tye-Din, J.; Jewell, D.; Hill, A. Antagonist and not-toxic variants of the dominant wheat gliadin T cell epitope in coeliac disease. Gut, 2006, 55, 485-91.
91. Xia, J.; Siegel, M.; Bergseng, E.; Sollid, L.; Khosla, C. Inhibition of HLA-DQ2 mediated antigen presentation by analogues of a high affinity 33-residue peptide from alpha2-glaidin. J. Am. Chem. Soc., 2006, 128, 1859-67.
92. Xia, J.; Bergseng, E.; Fleckenstein, B.; Siegel, M.; Kim, C.; Khosla, C.; Sollid, L. Cyclic and dimeric gluten peptide analogues inhibiting DQ2-mediated antige presentation in celiac disease. Bioorg. Med. Chem., 2007, 15, 6565-73.
93. Kapoerchan, V.; Wiesner, M.; Overhand, M.; van der Marel, G.; Koning, F.; Overkleeft, H. Design of azidoproline containing gluten peptides to suppress CD4+ T-cell responses associated with celiac disease. Bioorg. Med. Chem., 2008, 16, 2053-62.
94. De Vincenzi, M.; Gasbarrini, G.; Silano, V. A small peptide from durum wheat gliadin prevents cell agglutination induced by prolamin-peptides toxic in coeliac disease. Toxicology, 1997, 120, 207-13.
95. Silano, M.; Di Benedetto, R.; Trecca, A.; Arrabito, G.; Leonardi, F.; De Vincenzi, M. A decapeptide from durum wheat prevents celiac peripheral blood lymphocytes from activation by gliadin peptides. Pediatr. Res., 2007, 61, 67-71.
96. Silano, M.; Di Benedetto, R.; Maialetti, F.; De Vincenzi, A.; Calcaterra, R.; Trecca, A.; De Vincenzi, M. A 10-residue peptide from durum wheat promotes a shift from a Th1-type towards a Th2-type response in celiac disease. Am. J. Clin. Nutr., 2008, 87, 415-23.
97. Silano, M.; Leonardi, F.; Trecca, A.; Mancini, E.; Di Benedetto, R.; De Vincenzi, M. Prevention by a decapeptide from durum wheat of in vitro gliadin peptide-induced apoptosis in snall-bowel mucosa from coeliac patients. Scand. J. Gastroenterol., 2007, 42, 786-7.