The in vitro response to human fibroblast-derived extracellular matrix proteins is restricted by specific HLA class II genes. Relevance for coeliac disease.
Coeliac disease is an immunologic disease of the small intestine which is caused by ingestion of wheat gliadin, the disease-promoting agent. The disease associates strongly with the particular HLA type, HLA-DQA1*0501, DQB1*0201 alleles. Further specific autoantibodies against reticulin and endomysium are found in patients; these autoantibodies appear to be disease specific. An extracellular matrix noncollagenous protein reacts specifically with CD patients' serum immunoglobulin A and is the target of antireticulin antibodies. In this study the immune response to this matrix protein was analyzed in vitro in normal, healthy individuals. Our study shows that the immune response to Fb-CDAP is strictly regulated by the HLA-DR3, DQA1*0501, DQB1*0201 alleles, and that only those cells which were positive for these alleles produced an immune response. On the other hand, half of the cells positive for these HLA alleles were responders. Monoclonal antibodies to DR and DQ inhibited the response in an additive way, showing that both DR and DQ can act as an antigen-presenting structure. The immune response to gliadin has been shown to associate with the same HLA type as CD, but the association is not as strong. Our results show that the immune responses to Fb-CDAP can be generated in vitro in genetically predisposed persons in the absence of CD.
Jalava
T
T
Finnish Red Cross Blood Transfusion Service, Helsinki, Finland.
Mäki
M
M
Marttinen
A
A
Partanen
J
J
Koskimies
S
S
D000328:Adult; D002102:Cadaver; D002446:Celiac Disease / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D006681:HLA-D Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D013154:Spleen / Q000166:cytology
D016326:Extracellular Matrix Proteins; D006681:HLA-D Antigens