The gluten-host interaction.
Work continues to progress in the unravelling of the molecular interactions involved in the pathogenesis of coeliac disease. The immunogenetics of the disease implicate certain HLA DQ alleles as necessary for subsequent disease development. These HLA molecules have been shown to be necessary in the binding and presentation of gliadin peptides to antigen-specific T cells. Current work is examining the precise HLA-antigen interaction that may lead to the development of antigen-blocking agents. The isolation of antigen-specific T cells has led to the confirmation of a toxic T-cell epitope of the gliadin protein (residues 31-49) and it would appear likely that additional toxic epitopes may be similarly characterized in the near future. No common TCR motifs have so far been detected, although these may become apparent as this work progresses. The gliadin peptide sequence, residues 31-49, has now been demonstrated to be toxic in vivo. Additional toxic T-cell epitopes may also be present within gliadins, but this identification of a toxic gliadin sequence for the first time raises the possibility of future manipulation of the wheat genome (and other toxic cereals) that could lead to the development of new graminae cereals with the properties of wheat, but which do not induce toxicity in patients with coeliac disease.
Tighe
M R
MR
Division of Pharmacology, United Medical and Dental Schools of Guy's Hospital, London, UK.
Ciclitira
P J
PJ
D000938:Antigen-Presenting Cells / Q000276:immunology; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology*; D002874:Chromosome Mapping; D002523:Edible Grain / Q000009:adverse effects*; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D007583:Jejunum / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D005983:Glutens; D005903:Gliadin