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

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

Human Immunology

Volume 39, Issue 4, April 1994, Pages 243-252

https://doi.org/10.1016/0198-8859(94)90267-4 Get rights and content

Abstract

CD is unique among the HLA-associated diseases since (a) the disease-promoting agent (gliadin) is known and (b) the disease is precipitated mainly in individuals carrying a particular cis- or trans-encoded HLA-DQ heterodimer; i.e., DQ(α1^∗0501, β1^∗0201). Further, a preponderance of gliadin-specific T cells derived from the small intestinal mucosa of CD patients are restricted by this DQ heterodimer. T-cell recognition of gliadin peptides presented by the DQ(α1^∗, β1^∗0201) heterdimer may thus be of importance in CD. Here we report that a T-cell clone from a patient with CD recognizes a synthetic α-gliadin peptide, when presented by the cis- or trans-encoded CD-associated DQ(α1^∗0501, β1^∗0201) heterdimer. The minimal peptide recognized by the T-cell clone corresponds to residues 31–47 of α-gliadin, which is included in the part of α-gliadin previously shown to have disease-promoting activity. When testing analogue peptides derived from other α-gliadin sequences, one peptide differing by one amino acid was recognized by the T-cell clone, whereas the other peptide differing by two amino acids was not recognized. Our findings demonstrate that the CD-associated DQ(α1^∗0501, β1^∗0201) heterodimer may serve as an antigen-presenting molecule to T cells for certain gliadin peptides.

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In CD and CD-IgAD, the −308A allele was significantly more frequent than in controls, whereas no significant differences were observed for the biallelic polymorphisms at the −863 and for the three IL-10 promoter polymorphisms. The evaluation of combined TNF and IL-10 genotypes showed in CD-IgAD a significant reduction of −308G/−1082G homozygous subjects and both in CD and CD-IgAD groups an increase of 308AA/1082GG. Accordingly, CD-IgAD patients positive both for −308A TNF and −1082A IL-10 showed an increase of TNF-α and a reduction of IL-10 serum levels.
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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

Abstract

Gastroenterology

Gastroenterology

Hum Immunol

Gastroenterology

Hum Immunol

Hum Immunol

J Biol Chem

Lancet

Hum Immunol

Coeliac disease. II. The presence in wheat of a factor having a deleterious effect in cases of coeliac disease

Acta Pædiatr

Coeliac disease. IV. An investigation into the injurious constituents of wheat in connection with their action on patients with coeliac disease

Acta Pædiatr

Clinical testing of gliadin fractions in coeliac patients

Clin Sci

Coelic activity of the gliadin peptides CT-1 and CT-2

Z Lebensm Unters Forsch

Celiac sprue

N Engl J Med

Immunologic basis for celiac disease, inflammatory bowel disease, and type B chronic gastritis

Curr Opin Gastroenterol

Evidence for a primary association of celiac disease to a particular HLA-DQ α/β heterodimer

J Exp Med

Structural analysis of the HLA-DR, -DQ, and -DP alleles on the celiac disease-associated HLA-DR3 (DRw17) haplotype

T lymphocyte recognition of a celiac disease-associated cis- or trans-encoded HLA-DQ α/β heterodimer

J Immunol

Gliadin-specific, HLA-DQ(α1∗0501,β1∗0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients

J Exp Med

Diagnostic criteria in coeliac disease

Acta Paediatr Scand

Description of the reference panel of B-lymphoblastoid cell lines for factors of the HLA system: the B-cell line panel designed for the Tenth International Histocompatibility Workshop

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

Gliadin-specific, HLA-DQ(α1^∗0501,β1^∗0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients