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.