Is celiac disease due to molecular mimicry between gliadin peptide-HLA class II molecule-T cell interactions and those of some unidentified superantigen?

• Published in: Molecular immunology Vol. 34; no. 7; pp. 535 - 541
• Main Authors: Barbeau, William E., Novascone, Mary Ann, Elgert, Klaus D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.1997
• Subjects: Adenovirus E1B Proteins - chemistry; Animals; celiac disease; Celiac Disease - immunology; Dimerization; DR molecules; Gliadin - chemistry; Gliadin - immunology; gliadin peptides; Haploidy; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; HLA Antigens - genetics; HLA Antigens - immunology; HLA-DQ; Humans; Models, Immunological; Molecular Mimicry - immunology; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, Antigen, T-Cell, gamma-delta - immunology; Superantigens - chemistry; Superantigens - immunology; T-Lymphocytes - immunology; celiac disease; DR molecules; gliadin peptides; HLA-DQ
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/S0161-5890(97)00068-0

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 11 molecules distal to the peptide-binding groove invoking recognition and binding by specialized subsets of γδ T cell receptor-bearing lymphocytes. The binding of these γδ 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.