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
Kea. Lundin et al., 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, The Journal of experimental medicine, 178(1), 1993, pp. 187-196
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.