title: The functional link between the immune suppression gene and Mhc class II molecules.
abstract: The immune response to bovine insulin (BI) in the rat is controlled by the major histocompatibility complex (Mhc)-linked immune response gene (Ir-BI) and immune suppression gene (Is-BI). In the present study, we investigated the low responsiveness to BI in the WKAH rat (RT1k) and attempted to explore the functional link between Is-BI and Mhc class II molecules. Lymph node cells (LNC) from the low responder (WKAH) rats responded well to BI when a large amount of antigen was added to the culture in vitro or after OX8-bearing (OX8+) T cells were eliminated. These LNC, after the elimination of OX8+ cells, could show the RT1.Dk-restricted proliferative response upon in vitro challenge with BI, BI-B chain, or pork insulin. In addition, OX8+ T cells, which were activated with BI and antigen-presenting cells (APC) in vitro, suppressed the anti-BI response of W3/25-bearing proliferating T cells from BI-immunized rats. The results have demonstrated that proliferating T-cell repertoires do exist to BI, which recognize BI-B chain in the context of RT1.Dk molecules in the WKAH rat, and that the state of low responsiveness is mediated to a great extent by antigen-specific OX8+ suppressor T (Ts) cells. Furthermore, the elimination of APC or the addition to RT1.Bk-specific monoclonal antibody in the in vitro secondary activation culture of Ts cells diminished the suppressive activity of OX8+ Ts cells. In the induction phase of Ts cells it therefore seems to be necessary for these cells to recognize BI together with RT1.Bk molecules on APC.
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology; D002417:Cattle; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D007328:Insulin / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics* / Q000276:immunology; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000939:Epitopes; D007328:Insulin