Cristin-resultat-ID: 438767
Sist endret: 21. januar 2015 15:27
Resultat
Vitenskapelig artikkel
2001

T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase

Bidragsytere:
  • Øyvind Molberg
  • Stephen N. McAdam
  • Knut E. A. Lundin
  • C Kristiansen
  • Eva Helene Arentz-Hansen
  • Kjell Kett
  • mfl.

Tidsskrift

European Journal of Immunology
ISSN 0014-2980
e-ISSN 1521-4141
NVI-nivå 2

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2001
Volum: 31
Sider: 1317 - 1323

Importkilder

ForskDok-ID: 64320

Beskrivelse Beskrivelse

Tittel

T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase

Sammendrag

Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gliadins. Initial studies used gliadin that had been subjected to non-enzymatic deamidation during pepsin/trypsin digestion to enrich for the gliadin-specific T cells in small intestinal celiac biopsies. These T cells recognized synthetic gliadin peptides only after their deamidation in vitro by purified tissue transglutaminase (tTG). However, as these studies used a deamidated antigen for re-stimulation prior to testing for antigen specificity, this raised the possibility that T cells specific for native epitopes had not been expanded in vitro and had thus been overlooked. To address this possibility and to look for more direct evidence that endogenous tTG mediates deamidation of gluten in the celiac lesions, we have here used a minimally deamidated chymotrypsin-digest of gliadin to challenge biopsies and then investigated the specificity of the T cell lines derived from them. Interestingly, these T cell lines only barely responded to the chymotrypsin-digested gliadins, but efficiently recognized the in vitro tTG-treated variants of the same gliadins. Moreover, the addition of a tTG-inhibitor during the gliadin challenge often resulted in T cell lines with abolished or reduced responses to deamidated gliadin. These data demonstrate that DQ2-restricted T cells within adult celiac lesions predominantly recognize deamidated gliadin epitopes that are formed in situ by endogenous tTG.

Bidragsytere

Øyvind Molberg

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo

Stephen N. McAdam

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo

Knut E. A. Lundin

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo

C Kristiansen

  • Tilknyttet:
    Forfatter

Eva Helene Arentz-Hansen

  • Tilknyttet:
    Forfatter
    ved Immunologisk institutt ved Universitetet i Oslo
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