GENETIC-CONTROL OF ANTITHYROTROPIN RECEPTOR ANTIBODY GENERATION IN H-2(K) MICE IMMUNIZED WITH THYROTROPIN RECEPTOR TRANSFECTED FIBROBLASTS

We recently showed that immunization of AKR/N mice with murine fibrobl asts transfected with the thyrotropin receptor (TSHR) and a murine maj or histocompatibility complex (MHC) class II molecule having the same H-2(k) haplotype, but not either alone, induces immune thyroid disease with the humoral and histological features of human Graves', includin g the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs which cause hyperthyroidism and thyrotropin-binding-inhibitin g immunoglobulins (TBIIs). Immunization of 5 different mouse strains t hat share the H-2(k) haplotype, but differ in their genetic background , results in different TBII titers, indicating non-MHC genetic effect on TSHRAb formation. In addition, immunization of C3H/He mice induced TBII formation even in the absence of aberrant class II, unlike AKR/N mice. However, the mice did not develop hyperthyroxinemia characterist ic of the presence of stimulating TSHRAbs. Aberrant class II expressio n is, therefore, necessary for the development of a full Graves' syndr ome with stimulating TSHRAbs; and immune recognition mechanisms by whi ch TBIIs and stimulating TSHRAbs develop are differently regulated.