0161-5H90i97 %17.00 + n.no IS CELIAC DISEASE DUE TO MOLECULAR MIMICRY BETWEEN GLIADIN PEPTIDE-HLA CLASS II MOLECULE-T CELL INTERACTIONS AND THOSE OF SOME UNIDENTIFIED SUPERANTIGEN?

Abstract-This paper presents a new hypothesis for the etiology and pathogenesis of cehac disease (CD). It is our contention that CD is triggered by the binding of one or more gliadin peptides to CD-associated HLA class II molecules. Furthermore, we propose that these putative CD peptides bind to oligosaccharide residues on HLA class II molecules distal to the peptide-binding groove invoking recognition and binding by specialized subsets of;‘6 T cell receptor-bearing lymphocytes. The binding of these ~6 T cells serves as a signal for abrogation of oral tolerance to ingested proteins setting in motion a series of immune responses directed against the small intestinal epithelium of CD patients. CD patients are victimized by this self-destructed immune response because of inheritance of certain combinations of HLA-DQ and DR haplotypes. Dimers encoded by HLA-DR haplotypes may be the primary restriction elements for lectin-like, gliadin peptides while the degree of immune suppression (or lack thereof) to ingested gliadins is governed by inherited HLA-DQ haplotypes. Finally. we speculate that molecular mimicry between one or more gliadin peptides and some, as yet unidentified. bacterial or viral superantigen plays a role in disease pathogenesis. I ‘ 1997 Elsevier Science Ltd. Kc)>, words: celiac disease, gliadin peptides. HLA-DQ.- DR molecule