Is celiac disease due to molecular mimicry between gliadin peptide-HLA class II molecule-T cell interactions and those of some unidentified superantigen?
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 specialized subsets of gamma delta T cell receptor-bearing lymphocytes. The binding of these gamma delta 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-distructed 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.
Barbeau
W E
WE
Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg 24061-0430, USA.
Novascone
M A
MA
Elgert
K D
KD
D017501:Adenovirus E1B Proteins / Q000737:chemistry; D000818:Animals; D002446:Celiac Disease / Q000276:immunology*; D019281:Dimerization; D005903:Gliadin / Q000737:chemistry / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006238:Haploidy; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D018716:Molecular Mimicry / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D018089:Superantigens / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D017501:Adenovirus E1B Proteins; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018089:Superantigens; D005903:Gliadin