THE IN-VITRO RESPONSE TO HUMAN FIBROBLAST-DERIVED EXTRACELLULAR-MATRIX PROTEINS IS RESTRICTED BY SPECIFIC HLA CLASS-II GENES - RELEVANCE FOR CELIAC-DISEASE

Coeliac disease is an immunologic disease of tile small intestine whic h is caused by ingestion of wheat gliadin, the disease-promoting agent . The disease associates strongly with the particular HLA type, HLA-DQ A10501, DQB1*0201 alleles. Further specific autoantibodies against re ticulin and endomysium are found in patients; these autoantibodies app ear to be disease specific. An extracellular matrix noncollagenous pro tein reacts specifically with CD patients' serum immunoglobulin A and is the target of antireticulin antibodies. In this study the immune re sponse to this matrix protein was analyzed in vitro in normal, healthy individuals. Our study shows that the immune response to Fb-CDAP is s trictly regulated by the HLA-DR3, DQA10501, DQB1*0201 alleles, and th at only those cells which were positive for these alleles produced an immune response. On the other hand, half of the cells positive for the se HLA alleles were responders. Monoclonal antibodies to DR and DQ inh ibited the response in an additive way, showing that both DR and DO ca n act as an antigen-presenting structure. The immune response to gliad in has been shown io associate with the same HLA type as CD, bur the a ssociation is not as strong. Our results show that the immune response to Fb-CDAP can be generated in vitro in genetically predisposed perso ns in the absence of Cn.