Article
T cells from the peripheral blood of coeliac disease patients recognize gluten antigens when presented by HLA-DR, -DQ, or -DP molecules.
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
Scandinavian Journal of Immunology (impact factor:
2.23).
07/1994;
39(6):567-74.
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: Innate and adaptive immunity: the yin and yang of celiac disease.
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ABSTRACT: Celiac disease is a multigenetic complex inflammatory disorder with an autoimmune component, induced by gluten, a protein found in wheat. It is a unique human disease model to dissect the innate and adaptive immune mechanisms underlying T-cell-mediated tissue destruction and the development of T-cell lymphoma in conditions of chronic T-cell activation.Immunological Reviews 09/2005; 206:219-31. · 11.15 Impact Factor -
Article: Coeliac disease: dissecting a complex inflammatory disorder.
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ABSTRACT: The disease mechanisms of complex inflammatory disorders are difficult to define because of extensive interactions between genetic and environmental factors. Coeliac disease is a typical complex inflammatory disorder, but this disease is unusual in that crucial genetic and environmental factors have been identified. This knowledge has allowed functional studies of the predisposing HLA molecules, the identification of antigenic epitopes and detailed studies of disease-relevant T cells in coeliac disease. This dissection of the pathogenic mechanisms of coeliac disease has uncovered principles that are relevant to other chronic inflammatory diseases.Nature reviews. Immunology 10/2002; 2(9):647-55. · 33.29 Impact Factor -
Article: Molecular basis of celiac disease.
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ABSTRACT: Celiac disease (CD) is an intestinal disorder with multifactorial etiology. HLA and non-HLA genes together with gluten and possibly additional environmental factors are involved in disease development. Evidence suggests that CD4(+) T cells are central in controlling an immune response to gluten that causes the immunopathology, but the actual mechanisms responsible for the tissue damage are as yet only partly characterized. CD provides a good model for HLA-associated diseases, and insight into the mechanism of this disease may well shed light on oral tolerance in humans. The primary HLA association in the majority of CD patients is with DQ2 and in the minority of patients with DQ8. Gluten-reactive T cells can be isolated from small intestinal biopsies of celiac patients but not of non-celiac controls. DQ2 or DQ8, but not other HLA molecules carried by patients, are the predominant restriction elements for these T cells. Lesion-derived T cells predominantly recognize deamidated gluten peptides. A number of distinct T cell epitopes within gluten exist. DQ2 and DQ8 bind the epitopes so that the glutamic acid residues created by deamidation are accommodated in pockets that have a preference for negatively charged side chains. Evidence indicates that deamidation in vivo is mediated by the enzyme tissue transglutaminase (tTG). Notably, tTG can also cross-link glutamine residues of peptides to lysine residues in other proteins including tTG itself. This may result in the formation of complexes of gluten-tTG. These complexes may permit gluten-reactive T cells to provide help to tTG-specific B cells by a mechanism of intramolecular help, thereby explaining the occurrence of gluten-dependent tTG autoantibodies that is a characteristic feature of active CD.Annual Review of Immunology 02/2000; 18:53-81. · 52.76 Impact Factor
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Keywords
CD patients
Coeliac disease
different HLA class-II molecules
DP molecules
DQ molecules
gliadin specific T cells
gliadin-specific T cells
gluten
gluten antigens
gluten-derived peptides
gluten-specific T cells
Gluten-specific T-cell clones
immunological disease
similar T cells
small intestinal mucosa
small intestine
T-cell
T-cell responses
TCC
vitro