IS CELIAC-DISEASE DUE TO MOLECULAR MIMICRY BETWEEN GLIADIN PEPTIDE HLA CLASS-II MOLECULE T-CELL INTERACTIONS AND THOSE OF SOME UNIDENTIFIEDSUPERANTIGEN

This paper presents a new hypothesis for the etiology and pathogenesis of celiac 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 special ized subsets of gamma delta T cell receptor-bearing lymphocytes. The b inding of these gamma delta T cells serves as a signal for abrogation of oral tolerance to ingested proteins setting in motion a series of i mmune responses directed against the small intestinal epithelium of CD patients. CD patients are victimized by this self-destructed immune r esponse because of inheritance of certain combinations of HLA-DQ and D R haplotypes. Dimers encoded by HLA-DR haplotypes may be the primary r estriction elements for lectin-like, gliadin peptides while the degree of immune suppression (or lack thereof) to ingested gliadins is gover ned by inherited HLA-DQ haplotypes. Finally, we speculate that molecul ar mimicry between one or more gliadin peptides and some, as yet unide ntified, bacterial or viral superantigen plays a role in disease patho genesis. (C) 1997 Elsevier Science Ltd.