[Analysis of the functional link between the immune suppression gene and the MHC class II molecules].
The immune response to bovine insulin (BI) in the rat is under the control of the major histocompatibility complex (MHC) linked immune response gene (Ir-BI) and immune suppression gene (Is-BI). In the present study, a possible mechanism of the low responsiveness to BI in the WKAH rat (RT1k) was investigated. Lymph node cells (LNC) from the low responder (WKAH) rats could respond well to BI when a large amount of antigen was added into in vitro culture or after OX8 bearing (OX8+) T cells were eliminated. These OX8+ cells-depleted LNC 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 secondary 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 there do exist proliferating T cell repertoire(s) 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 mostly by OX8+ suppressor T (Ts) cells. Furthermore, the elimination of APC or the addition of an anti-RT1.Bk monoclonal antibody into the in vitro secondary priming culture of Ts cells diminished the suppressive activity of OX8+ Ts cells. Therefore, in the induction phase of Ts cells, it has appeared to be necessary for these cells to recognize BI together with RT1.Bk molecules on APC. Finally, OX8+ Ts cells appear to recognize BI-A chain since LNC from immunized rats could respond well to BI-B chain but not to BI whole molecules. The functional link between Is-BI and MHC-class II molecules is discussed.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000939:Epitopes / Q000032:analysis; D005260:Female; D005802:Genes, MHC Class II; D007328:Insulin / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000939:Epitopes; D007328:Insulin