RT1-linked Ir and Is genes control the immune response to bovine insulin in the rat

The immune response to bovine or pork insulin (BI or PI, respectively) was studied in the rat using the in vitro insulin-induced lymphocyte-proliferation assay. Results indicated that 11 inbred rat strains were divided into categories of high and low responders. Two high responders, SDJ (RT1u) and BN(RT1n) inbred rat strains, appeared to recognize different antigenic determinant(s) on the insulin molecule. The results of linkage and segregation analyses in F1, F2, backcross, and partially congenic rats showed that the Ir gene (Ir-BI), which encodes the high responsiveness in the SDJ rats, is inherited associated with RT1u, whereas the immune suppression gene (Is-BI), which encodes the low responsiveness in the WKA(RT1k) rats, is inherited together with RT1k. The Is-BI is the first major histocompatibility complex (MHC)-linked Is gene reported in the rat. The LEJ(RT1-AuBb) inbred rat strain showed a low response to BI, indicating that Ir-BI is closer to RT1-B/RT1-D region than to RT1-A.