Translocation of gliadin into HLA-DR antigen containing lysosomes in coeliac disease enterocytes.
Coeliac disease is triggered by ingestion of wheat gliadin and is probably immune mediated. There is evidence by light microscopy that expression of class II major histocompatibility complex (MHC) molecules is increased in the small intestinal epithelium of patients with untreated coeliac disease and that gliadin can be taken up by small intestinal enterocytes. The pathway by which gliadin is transported to class II MHC proteins has not been demonstrated. Using an immunogold technique and thin frozen sections of jejunal biopsy specimens, gliadin, HLA-DR antigens, and IgA were localised at an ultrastructural level in the jejunal epithelium of patients with both untreated and treated coeliac disease and controls. Cathepsin D was used as a marker for late endosomes or lysosomes. The results show that gliadin is translocated into vacuoles positive for HLA-DR antigens as well as cathepsin D in jejunal enterocytes of patients with untreated coeliac disease. Secretory IgA may have a role in this translocation of gliadin, which is a specific event that occurred only in jejunal enterocytes from patients with untreated coeliac disease but not in a patient maintained on a gluten free diet or in controls. These results support a central role for epithelial cells of the human intestinal mucosa in the transport of gliadin to an HLA-DR positive compartment which precedes antigen presentation of gliadin to antigen sensitive T lymphocytes.
Zimmer
K P
KP
University Children's Hospital, Münster, Germany.
Poremba
C
C
Weber
P
P
Ciclitira
P J
PJ
Harms
E
E
D017951:Antigen Presentation; D002402:Cathepsin D / Q000032:analysis; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis; D005903:Gliadin / Q000032:analysis / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000032:analysis / Q000378:metabolism*; D008247:Lysosomes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016253:Microscopy, Immunoelectron
D006684:HLA-DR Antigens; D007071:Immunoglobulin A, Secretory; D005903:Gliadin; D002402:Cathepsin D