T cells recognize a peptide derived from α-gliadin presented by the celiac disease-associated HLA-DQ (α1∗0501, β1∗0201) heterodimer

Gjertsen, Henrik; Lundin, Knut E.A.; Sollid, Ludvig M.; Eriksen, Jon Amund; Thorsby, E.

doi:10.1016/0198-8859(94)90267-4

Cited by 71 publications

(51 citation statements)

References 36 publications

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“…Several studies have reported that naturally occurring gliadin epitopes cannot be recognized by T cells cloned from the intestinal mucosa patients with established disease, although they are recognized by T cells derived from peripheral blood (37)(38)(39). The assertion that deamidation of the gliadin peptides is essential to celiac disease is based almost exclusively on results of experiments in which T cells cloned from the active established lesion of celiac disease are used as a measure of responsiveness (10 -12, 24, 39 -43).…”

Section: Discussionmentioning

confidence: 99%

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

Black¹,

Murray

David³

2002

The Journal of Immunology

136

107

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We have investigated the genetic basis of the immune response to dietary gluten in HCD4/DQ8 and HCD4/DQ6 double transgenic mice. Mice were immunized with gluten i.p. or individual peptides s.c. and spleen or draining lymph node T cells were challenged in vitro. Strong proliferative responses to gluten were seen in the HCD4/DQ8 mice, whereas the HCD4/DQ6 mice responded to gluten poorly. A series of overlapping peptides spanning gliadin were synthesized. The HCD4/DQ8 mice reacted to many of the individual peptides of gliadin, while the HCD4/DQ6 mice were relatively unresponsive. T cells isolated from HCD4/DQ8 mice also responded well to modified (deamidated) versions of the gliadin peptides, whereas HCD4DQ6 mice did not. The T cell response to gluten was CD4 dependent and DQ restricted and led to the production of cytokines IL-6, TGF-β, and IL-10. Finally, intestinal lymphocytes isolated from gluten-fed HCD4/DQ8 mice displayed an activated phenotype. These data suggest that this HLA class II transgenic murine model of gluten sensitivity may provide insight into the initiation of the MHC class II-restricted gluten sensitivity in celiac disease.

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Section: Discussionmentioning

confidence: 99%

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

Black¹,

Murray

David³

2002

The Journal of Immunology

136

107

View full text Add to dashboard Cite

show abstract

“…After an in vitro gluten challenge, cells were isolated from four treated (gluten-free diet) patients with coeliac disease and from four healthy controls [12][13][14]. Of the 21 gluten-reactive TCC established from the coeliac patients, 11 were restricted by the diseaseassociated HLA-DQ2 heterodimer, whereas 10 were HLA-DRrestricted (both DR3, DR4 and DR7); of the six studied glutenreactive TCC established from two healthy individuals, four were DQ2-restricted, whereas two were DR4-restricted.…”

Section: Discussionmentioning

confidence: 99%

“…Gluten-reactive peripheral blood TCC were prepared from four treated coeliac patients and four healthy individuals, as detailed elsewhere [12][13][14]. All carried HLA-DR3 (DRB1*0301) as well as HLA-DQ2 (DQA1*0501, DQB1*0201) and in most cases a non-DR3, DQ2 haplotype.…”

Section: T Cell Clonesmentioning

confidence: 99%

Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls

Nilsen

Gjertsen

Jensen

et al. 1996

Clinical and Experimental Immunology

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SUMMARYCoeliac disease is apparently a T cell-mediated disease, precipitated in the proximal small intestine of susceptible individuals by gluten. Preferential presentation of gluten peptides most probably takes place in coeliac mucosa by the disease-associated HLA-DQ2 and -DQ8 molecules. In peripheral blood, however, both HLA-DR, -DQ and -DP-restricted T cell responses to gluten have been observed. We examined gluten-specific T cell clones (TCC) derived from peripheral blood for cytokine production to see if their profiles were related to the HLA restriction or the disease state of the donors. As previously found for mucosal TCC, the main product was interferon-gamma (IFN-), often with additional IL-4, IL-5, IL-6, IL-10, tumour necrosis factor, and transforming growth factor-beta. Regardless of restriction element or disease state, gluten-reactive TCC from peripheral blood therefore seem to secrete cytokines compatible with a Th0 profile.

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“…The DR7 association with celiac disease has been more often reported from southern Europe, due to an increased frequency of the DR5/7 genotype in these populations. That gliadin induces immune system activation is supported by the presence of giadin-specific, DQ2-restricted T-cells in the mucosa of celiac disease patients and the detection of anti-gliadin, anti-reticulin, and antiendomysial autoantibodies whose expression depends upon gliadin ingestion (37,38). Removal of gliadin from the diet results not only in resolution of the intestinal lesions but also the disappearance of the autoantibodies.…”

Section: 2addison's Diseasementioning

confidence: 99%

High-throughput radioassays for autoantibodies to recombinant autoantigens

Eisenbarth¹

2000

Front Biosci

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T cells recognize a peptide derived from α-gliadin presented by the celiac disease-associated HLA-DQ (α1∗0501, β1∗0201) heterodimer

Cited by 71 publications

References 36 publications

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

HLA-DQ Determines the Response to Exogenous Wheat Proteins: A Model of Gluten Sensitivity in Transgenic Knockout Mice

Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls

High-throughput radioassays for autoantibodies to recombinant autoantigens

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