The immune recognition of gluten in coeliac disease.
Coeliac disease, the most common intestinal disorder of western populations, is an autoimmune enteropathy caused by an abnormal immune response to dietary gluten peptides that occurs in genetically susceptible individuals carrying the HLA-DQ2 or -DQ8 haplotype. Despite the recent progresses in understanding the molecular mechanisms of mucosal lesions, it remains unknown how increased amounts of gluten peptides can enter the intestinal mucosa to initiate the inflammatory cascade. Current knowledge indicates that different gluten peptides are involved in the disease process in a different manner, some fragments being 'toxic' and others 'immunogenic'. Those defined as 'toxic' are able to induce mucosal damage either when added in culture to duodenal endoscopic biopsy or when administered in vivo, while those defined as 'immunogenic' are able to specifically stimulate HLA-DQ2- or DQ8-restricted T cell clones isolated from jejunal mucosa or peripheral blood of coeliac patients. These peptides are able to trigger two immunological pathways: one is thought to be a rapid effect on the epithelium that involves the innate immune response and the other represents the adaptive immune response involving CD4+ T cells in the lamina propria that recognize gluten epitopes processed and presented by antigen presenting cells. These findings are the subject of the present review.
Ciccocioppo
R
R
First Department of Internal Medicine, IRCCS Policlinico San Matteo, University of Pavia, Italy.
Di Sabatino
A
A
Corazza
G R
GR
D002446:Celiac Disease / Q000276:immunology*; D004044:Dietary Proteins / Q000276:immunology; D002523:Edible Grain / Q000276:immunology; D004848:Epithelium / Q000276:immunology; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology
D004044:Dietary Proteins; D006680:HLA Antigens; D010455:Peptides; D005983:Glutens; D005903:Gliadin