Heterogeneous reactivity patterns of HLA-DQ-restricted, small intestinal T-cell clones from patients with celiac disease

Abstract

Background & aims: T-cell immune reactions toward wheat gliadins seem important in the pathogenesis of celiac disease. We have previously shown that gliadin-specific T-cell clones (TCCs) from the small intestinal mucosa of patients with celiac disease are predominantly restricted by the celiac disease-associated HLA-DQ2 and HLA-DQ8 molecules, suggesting a link between the HLA association and immunopathogenesis. The aim of the present study was to investigate the nature of the stimulating gliadin antigens.

Methods: Three different pools of gliadins and one purified alpha-type and two purified gamma-type gliadin preparations were prepared by ion exchange chromatography and tested for recognition by a panel of small intestinal gliadin-specific TCCs.

Results: Evidence suggested that enzymatic digestion and heating of the gliadins influenced TCC stimulation. Most of the TCCs recognized all three gliadin pools, but some had distinct reactivity patterns. Thirteen of 21 TCCs responded to one or more of the three purified gliadins discerning highly discriminative patterns.

Conclusions: Small intestinal, gliadin-specific 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 disease.