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Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients

Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA- DQ(alpha 1*0501,beta 1*0201) (...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1993
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191064/
https://www.ncbi.nlm.nih.gov/pubmed/8315377
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description Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA- DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen- presenting molecule was established to be the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) V alpha and V beta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha 1*0501, beta 1*0201) in CD, which may explain the HLA association.
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spelling pubmed-21910642008-04-16 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 Articles Celiac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA- DQ(alpha 1*0501,beta 1*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen- presenting molecule was established to be the CD-associated DQ(alpha 1*0501, beta 1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) V alpha and V beta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha 1*0501, beta 1*0201) in CD, which may explain the HLA association. The Rockefeller University Press 1993-07-01 /pmc/articles/PMC2191064/ /pubmed/8315377 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
title Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
title_full Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
title_fullStr Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
title_full_unstemmed Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
title_short Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients
title_sort gliadin-specific, hla-dq(alpha 1*0501,beta 1*0201) restricted t cells isolated from the small intestinal mucosa of celiac disease patients
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191064/
https://www.ncbi.nlm.nih.gov/pubmed/8315377