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

Celiac disease (CD) is most probably an immunological disease, precipi tated in susceptible individuals by ingestion of wheat gliadin and rel ated proteins from other cereals. The disease shows a strong human HLA association predominantly to the cis or trans encoded HLA-DQ(alpha10 501,beta10201) (DQ2) heterodimer. T cell recognition of gliadin prese nted by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult C D patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25+ T cel ls. Polyclonal T cell lines and a panel of T cell clones recognizing g luten 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 mol ecules. The main antigen-presenting molecule was established to be the CD-associated DQ(alpha10501,beta1*0201) heterodimer. The gluten-reac tive T cell clones were CD4+, CD8-, and carried diverse combinations o f T cell receptor (TCR) Valpha and Vbeta chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ (alpha10501,beta1*0201) in CD, which may explain the HLA association.