HLA-DR3- and HLA-DR7-restricted T-cell hyporesponsiveness to gluten antigen: a clue to the aetiology of coeliac disease?
Coeliac disease (CD) is strongly associated with the human class-II HLA determinants HLA-DR3 and -DR7. We investigated the relative frequency of gluten-reactive T cells from DR3- or DR7-positive. CD patients and healthy controls who were heterozygous at the DR locus. We found a consistently and significantly lower frequency of gluten-reactive T cells when the antigen was presented by monocytes in conjunction with DR3 or DR7 than in conjunction with the other DR determinant of the T-cell donor. In contrast, the frequency of reactive T cells in these donors to other antigens was not reduced in conjunction with DR3 or DR7. These results indicate a specific immunoregulatory function associated with class-II HLA molecules. The reduced frequency of gluten-reactive T cells in association with HLA-DR3 or -DR7 may be directly involved in the development of CD.
D000941:Antigens / Q000276:immunology; D002446:Celiac Disease / Q000209:etiology / Q000276:immunology*; D005983:Glutens / Q000276:immunology; D015803:HLA-DR3 Antigen; D015809:HLA-DR7 Antigen; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D015803:HLA-DR3 Antigen; D015809:HLA-DR7 Antigen; D000949:Histocompatibility Antigens Class II; D005983:Glutens