Information de reference pour ce titreAccession Number: | 00004686-200608000-00027.
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Author: | Tollefsen, Stig 1; Arentz-Hansen, Helene 1; Fleckenstein, Burkhard 1; Molberg, Oyvind 1,2; Raki, Melinda 1; Kwok, William W. 3; Jung, Gunther 4; Lundin, Knut E.A. 1,5; Sollid, Ludvig M. 1
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Institution: | (1)Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. (2)Department of Rheumatology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. (3)Benaroya Research Institute, Seattle, Washington, USA. (4)Institute of Organic Chemistry, University of Tubingen, Tubingen, Germany. (5)Department of Medicine, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
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Title: | HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease.[Article]
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Source: | Journal of Clinical Investigation. 116(8):2226-2236, August 2006.
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Abstract: | Celiac disease is associated with HLA-DQ2 and, to a lesser extent, HLA-DQ8. Type 1 diabetes is associated with the same DQ molecules in the opposite order and with possible involvement of trans-encoded DQ heterodimers. T cells that are reactive with gluten peptides deamidated by transglutaminase 2 and invariably restricted by DQ2 or DQ8 can be isolated from celiac lesions. We used intestinal T cells from celiac patients to map DQ2 and DQ8 epitopes within 2 representative gluten proteins, [alpha]-gliadin AJ133612 and [gamma]-gliadin M36999. For [alpha]-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of 2 separate regions. For [gamma]-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of the same region. Some [gamma]-gliadin peptides were recognized by T cells in the context of DQ2 or DQ8 when bound in exactly the same registers, but with different requirements for deamidation; deamidation at peptide position 4 (P4) was important for DQ2-restricted T cells, whereas deamidation at P1 and/or P9 was important for DQ8-restricted T cells. Peptides combining the DQ2 and DQ8 signatures could be presented by DQ2, DQ8, and trans-encoded DQ heterodimers. Our findings shed light on the basis for the HLA associations in celiac disease and type 1 diabetes.
Copyright (C) 2006 The American Society for Clinical Investigation, Inc.
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References: | 1. Green P.H., and Jabri B. 2003. Coeliac disease. Lancet. 362:383-391.
2. Sollid L.M. 2000. Molecular basis of celiac disease. Annu. Rev. Immunol. 18:53-81.
3. Sollid L.M., and Lie B.A. 2005. Celiac disease genetics: current concepts and practical applications. Clin. Gastroenterol. Hepatol. 3:843-851.
4. Lundin K.E.A., et al. 1993. Gliadin-specific, HLA-DQ([alpha]1*0501,[beta]1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J. Exp. Med. 178:187-196.
5. Molberg O., et al. 1997. Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls. Scand. J. Immunol. 46:103-109.
6. Lundin K.E.A., Scott H., Fausa O., Thorsby E., and Sollid L.M. 1994. T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8. Hum. Immunol. 41:285-291.
7. Molberg O., et al. 1998. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells. Nat. Med. 4:713-717.
8. van de Wal Y., et al. 1998. Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J. Immunol. 161:1585-1588.
9. Johansen B.H., Vartdal F., Eriksen J.A., Thorsby E., and Sollid L.M. 1996. Identification of a putative motif for binding of peptides to HLA-DQ2. Int. Immunol. 8:177-182.
10. van de Wal Y., Kooy Y.M.C., Drijfhout J.W., Amons R., and Koning F. 1996. Peptide binding characteristics of the coeliac disease-associated DQ([alpha]1*0501, [beta]1*0201) molecule. Immunogenetics. 44:246-253.
11. Kwok W.W., Domeier M.L., Raymond F.C., Byers P., and Nepom G.T. 1996. Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase. J. Immunol. 156:2171-2177.
12. Godkin A., et al. 1997. Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2). Int. Immunol. 9:905-911.
13. Suri A., Walters J.J., Gross M.L., and Unanue E.R. 2005. Natural peptides selected by diabetogenic DQ8 and murine I-A(g7)molecules show common sequence specificity. J. Clin. Invest. 115:2268-2276 10.1172/JCI25350.
14. Sjostrom H., et al. 1998. Identification of a gliadin T-cell epitope in coeliac disease: general importance of gliadin deamidation for intestinal T-cell recognition. Scand. J. Immunol. 48:111-115.
15. Arentz-Hansen H., et al. 2000. 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. 191:603-612.
16. Anderson R.P., Degano P., Godkin A.J., Jewell D.P., and Hill A.V. 2000. In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope. Nat. Med. 6:337-342.
17. Vader W., et al. 2002. The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology. 122:1729-1737.
18. Arentz-Hansen H., et al. 2002. Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues. Gastroenterology. 123:803-809.
19. Qiao S.W., et al. 2005. 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. 175:254-261.
20. van de Wal Y., et al. 1998. Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin. Proc. Natl. Acad. Sci. U. S. A. 95:10050-10054.
21. van de Wal Y., et al. 1999. Glutenin is involved in the gluten-driven mucosal T cell response. Eur. J. Immunol. 29:3133-3139.
22. Svejgaard A., and Ryder L.P. 1981. HLA genotype distribution and genetic models of insulin-dependent diabetes mellitus. Ann. Hum. Genet. 45:293-298.
23. Todd J.A., Bell J.I., and McDevitt H.O. 1987. HLA-DQ[beta] gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 329:599-604.
24. Thorsby E. 1997. Invited anniversary review: HLA associated diseases. Hum. Immunol. 53:1-11.
25. Nepom G.T., and Erlich H. 1991. MHC class-II molecules and autoimmunity. Annu. Rev. Immunol. 9:493-525.
26. Redondo M.J., and Eisenbarth G.S. 2002. Genetic control of autoimmunity in type I diabetes and associated disorders. Diabetologia. 45:605-622.
27. Koeleman B.P.C., et al. 2004. Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer associations with disease. Genes Immun. 5:381-388.
28. Lee K.H., Wucherpfennig K.W., and Wiley D.C. 2001. Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes. Nat. Immunol. 2:501-507.
29. Kim C.Y., Quarsten H., Bergseng E., Khosla C., and Sollid L.M. 2004. Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease. Proc. Natl. Acad. Sci. U. S. A. 101:4175-4179.
30. Jones E.Y., Fugger L., Strominger J.L., and Siebold C. 2006. MHC class II proteins and disease: a structural perspective. Nat. Rev. Immunol. 6:271-282.
31. Bergseng E., Xia J., Kim C.Y., Khosla C., and Sollid L.M. 2005. Main chain hydrogen bond interactions in the binding of proline-rich gluten peptides to the Celiac disease-associated HLA-DQ2 molecule. J. Biol. Chem. 280:21791-21796.
32. Nelson C.A., and Fremont D.H. 1999. Structural principles of MHC class II antigen presentation. Rev. Immunogenet. 1:47-59.
33. Nepom B.S., Schwarz D., Palmer J.P., and Nepom G.T. 1987. Transcomplementation of HLA genes in IDDM. HLA-DQ [alpha]- and [beta]-chains produce hybrid molecules in DR3/4 heterozygotes. Diabetes. 36:114-117.
34. Kwok W.W., Kovats S., Thurtle P., and Nepom G.T. 1993. HLA-DQ allelic polymorphisms constrain patterns of class II heterodimer formation. J. Immunol. 150:2263-2272.
35. Peakman M., et al. 2001. Characterization of preparations of GAD65, proinsulin, and the islet tyrosine phosphatase IA-2 for use in detection of autoreactive T-cells in type 1 diabetes: report of phase II of the Second International Immunology of Diabetes Society Workshop for Standardization of T-cell assays in type 1 diabetes. Diabetes. 50:1749-1754.
36. Viglietta V., Kent S.C., Orban T., and Hafler D.A. 2002. GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes. J. Clin. Invest. 109:895-903 10.1172/JCI200214114.
37. Kent S.C., et al. 2005. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature. 435:224-228.
38. Mannering S.I., et al. 2005. The insulin A-chain epitope recognized by human T cells is posttranslationally modified. J. Exp. Med. 202:1191-1197.
39. Arentz-Hansen E.H., McAdam S.N., Molberg O., Kristiansen C., and Sollid L.M. 2000. Production of a panel of recombinant gliadins for the characterisation of T cell reactivity in coeliac disease. Gut. 46:46-51.
40. Molberg O., et al. 2003. Intestinal T-cell responses to high-molecular-weight glutenins in celiac disease. Gastroenterology. 125:337-344.
41. Piper J.L., Gray G.M., and Khosla C. 2002. High selectivity of human tissue transglutaminase for immunoactive gliadin peptides: implications for celiac sprue. Biochemistry. 41:386-393.
42. Viken H.D., et al. 1995. Characterization of an HLA-DQ2-specific monoclonal antibody. Influence of amino acid substitutions in DQ[beta]1*0202. Hum. Immunol. 42:319-327.
43. Giles R.C., et al. 1983. Structural analysis of a human I-A homologue using a monoclonal antibody that recognizes an MB3-like specificity. J. Exp. Med. 157:1461-1470.
44. Spits H., Ijssel H., Thompson A., and De Vries J.E. 1983. Human T4+ and T8+ cytotoxic T lymphocyte clones directed at products of different class II major histocompatibility complex loci. J. Immunol. 131:678-683.
45. Amar A., et al. 1987. Characterization of specific HLA-DQ[alpha] allospecificities by genomic, biochemical, and serologic analysis. J. Immunol. 138:3986-3990.
46. Kwok W.W., et al. 1988. HLA-DQ molecules form [alpha]-[beta] heterodimers of mixed allotype. J. Immunol. 141:3123-3127.
47. Reichstetter S., Kwok W.W., and Nepom G.T. 1999. Impaired binding of a DQ2 and DQ8-binding HSV VP16 peptide to a DQA1*0501/DQB1*0302 trans class II heterodimer. Tissue Antigens. 53:101-105.
48. Molberg, O., McAdam, S.N., Lundin, K.E.A., and Sollid, L.M. 2000. Studies of gliadin-specific T cells in celiac disease. In Celiac disease. Methods and protocols. M.N. Marsh, editor. Humana. Totowa, New Jersey, USA. 105-124.
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Language: | English.
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Document Type: | Research Article.
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Journal Subset: | Clinical Medicine. Life Sciences.
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ISSN: | 0021-9738
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NLM Journal Code: | hs7, 7802877
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