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| GLIADIN-SPECIFIC, HLA-DQ(ALPHA-1-ASTERISK-0501,BETA-1-ASTERISK-0201) RESTRICTED T-CELLS ISOLATED FROM THE SMALL-INTESTINAL MUCOSA OF CELIAC-DISEASE PATIENTS |
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| Author(s): LUNDIN KEA, SCOTT H, HANSEN T, PAULSEN G, HALSTENSEN TS, FAUSA O, THORSBY E, SOLLID LM |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 178 Issue: 1 Pages: 187-196 Published: JUL 1 1993 |
| Times Cited: 303 References: 50 |
| Abstract: 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(alpha1*0501,beta1*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(alpha1*0501,beta1*0201) heterodimer. The gluten-reactive T cell clones were CD4+, CD8-, and carried diverse combinations of T cell receptor (TCR) Valpha and Vbeta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(alpha1*0501,beta1*0201) in CD, which may explain the HLA association. |
| Document Type: Article |
| Language: English |
| Reprint Address: LUNDIN, KEA (reprint author), NATL HOSP NORWAY, INST TRANSPLANTAT IMMUNOL, N-0027 OSLO, NORWAY |
Addresses:
1. NATL HOSP NORWAY, MED DEPT A, GASTROENTEROL SECT, N-0027 OSLO, NORWAY
2. NATL HOSP NORWAY, INST PATHOL, IMMUNOHISTOCHEM & IMMUNOPATHOL LAB, N-0027 OSLO, NORWAY
3. UNIV OSLO, N-0027 OSLO, NORWAY |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: LH549 |
| ISSN: 0022-1007 |
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