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PMID: 9707598 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 17 ·1998-08-18 ·Pages 10050-4

van de Wal Y, Kooy YM, van Veelen PA, Peña SA, Mearin LM, Molberg O, Lundin KE, Sollid LM, Mutis T, Benckhuijsen WE, Drijfhout JW, Koning F

Abstract

Celiac disease is a common severe intestinal disease resulting from intolerance to dietary wheat gluten and related proteins. The large majority of patients expresses the HLA-DQ2 and/or DQ8 molecules, and gluten-specific HLA-DQ-restricted T cells have been found at the site of the lesion in the gut. The nature of peptides that are recognized by such T cells, however, has been unclear so far. We now report the identification of a gliadin-derived epitope that dominantly is recognized by intestinal gluten-specific HLA-DQ8-restricted T cells. The characterization of such epitopes is a key step toward the development of strategies to interfere in mechanisms involved in the pathogenesis of celiac disease.

MeSH Terms
Amino Acid Sequence Celiac Disease/etiology,immunology,pathology Clone Cells Gliadin/chemistry,genetics,immunology HLA-DQ Antigens Humans Immunodominant Epitopes/chemistry,genetics Intestinal Mucosa/immunology,pathology Intestine, Small/immunology,pathology Lymphocyte Activation Molecular Sequence Data Pepsin A Peptide Fragments/chemistry,genetics,immunology T-Lymphocytes/immunology,pathology
Chemicals
HLA-DQ Antigens HLA-DQ2 antigen HLA-DQ8 antigen Immunodominant Epitopes Peptide Fragments Gliadin Pepsin A
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
van de Wal Y
Department of Immunohaematology and Bloodbank, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [email protected]
Kooy Y M
van Veelen P A
Peña S A
Mearin L M
Molberg O
Lundin K E
Sollid L M
Mutis T
Benckhuijsen W E
Drijfhout J W
Koning F
References (21)
21 references, click to expand
  1. Possible role for a human adenovirus in the pathogenesis of celiac disease.
    J Exp Med. 1984 Nov 1;160(5):1544-57 PMID: 6491604
  2. Coeliac disease. IV. An investigation into the injurious constituents of wheat in connection with their action on patients with coeliac disease.
    Acta Paediatr. 1953 May;42(3):223-31 PMID: 13079757
  3. Cell-mediated immunity to a synthetic gliadin peptide resembling a sequence from adenovirus 12.
    Lancet. 1987 Apr 18;1(8538):884-6 PMID: 2882290
  4. In vitro (organ culture) studies of the toxicity of specific A-gliadin peptides in celiac disease.
    Gastroenterology. 1988 Jan;94(1):41-9 PMID: 3335296
  5. In vivo toxicity of a synthetic dodecapeptide from A gliadin in patients with coeliac disease.
    Scand J Gastroenterol. 1991 Apr;26(4):392-8 PMID: 1827928
  6. Celiac sprue.
    N Engl J Med. 1991 Dec 12;325(24):1709-19 PMID: 1944472
  7. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue').
    Gastroenterology. 1992 Jan;102(1):330-54 PMID: 1727768
  8. 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. 1993 Jul 1;178(1):187-96 PMID: 8315377
  9. HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis.
    Gastroenterology. 1993 Sep;105(3):910-22 PMID: 8359659
  10. Wheat peptide challenge in coeliac disease.
    Lancet. 1994 Mar 26;343(8900):758-61 PMID: 7907731
  11. Peripheral T cell response to A-gliadin in celiac disease: differential processing and presentation capacities of Epstein-Barr-transformed B cells and fibroblasts.
    Clin Immunol Immunopathol. 1994 Apr;71(1):75-81 PMID: 7511085
  12. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
    J Exp Med. 1994 Apr 1;179(4):1109-18 PMID: 8145033
  13. T cells recognize a peptide derived from alpha-gliadin presented by the celiac disease-associated HLA-DQ (alpha 1*0501, beta 1*0201) heterodimer.
    Hum Immunol. 1994 Apr;39(4):243-52 PMID: 7520895
  14. Error-tolerant identification of peptides in sequence databases by peptide sequence tags.
    Anal Chem. 1994 Dec 15;66(24):4390-9 PMID: 7847635
  15. 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. 1994 Dec;41(4):285-91 PMID: 7883596
  16. Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma.
    Gut. 1995 Dec;37(6):766-76 PMID: 8537046
  17. Peptide binding characteristics of the coeliac disease-associated DQ(alpha1*0501, beta1*0201) molecule.
    Immunogenetics. 1996;44(4):246-53 PMID: 8753854
  18. Heterogeneous reactivity patterns of HLA-DQ-restricted, small intestinal T-cell clones from patients with celiac disease.
    Gastroenterology. 1997 Mar;112(3):752-9 PMID: 9041236
  19. Transglutaminase, gluten and celiac disease: food for thought. Transglutaminase is identified as the autoantigen of celiac disease.
    Nat Med. 1997 Jul;3(7):725-6 PMID: 9212095
  20. Identification of tissue transglutaminase as the autoantigen of celiac disease.
    Nat Med. 1997 Jul;3(7):797-801 PMID: 9212111
  21. Coeliac activity of the gliadin peptides CT-1 and CT-2.
    Z Lebensm Unters Forsch. 1986 Feb;182(2):115-7 PMID: 3705771
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.17.10050
Email
[email protected]
Published
1998-08-18
Pages
10050-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21459
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.17.10050 PMC Full Text View journal details
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