HETEROGENEOUS REACTIVITY PATTERNS OF HLA-DQ-RESTRICTED, SMALL-INTESTINAL T-CELL CLONES FROM PATIENTS WITH CELIAC-DISEASE

Background & Aims: T-cell immune reactions toward wheat gliadins seem important in the pathogenesis of celiac disease. We have previously sh own that gliadin-specific T-cell clones (TCCs) from the small intestin al mucosa of patients with celiac disease are predominantly restricted by the celiac disease-associated HLA-DQ2 and HLA-DQ8 molecules, sugge sting a link between the HLA association and immunopathogenesis. The a im of the present study was to investigate the nature of the stimulati ng gliadin antigens. Methods: Three different pools of gliadins and on e purified a-type and two purified gamma-type gliadin preparations wer e prepared by ion exchange chromatography and tested for recognition b y a panel of small intestinal gliadin-specific TCCs. Results: Evidence suggested that enzymatic digestion and heating of the gliadins influe nced TCC stimulation. Most of the TCCs recognized all three gliadin po ols, but some had distinct reactivity patterns. Thirteen of 21 TCCs re sponded to one or move of the three purified gliadins discerning highl y discriminative patterns. Conclusions: Small intestinal, gliadin-spec ific T cells from patients with celiac disease show diverse reactivity patterns. Stimulation of large numbers of different gliadin-specific T cells in the small intestinal mucosa of patients with celiac disease may occur; this may be an important immunopathogenic step in the dise ase.