Experimental autoimmune thyroiditis (EAT) is induced in certain mouse strains by injection of mouse thyroglobulin (MTg) with a suitable adjuvant (Rose et al. 1971). The severity of thyroiditis can be ascertained by the extent of mononuclear cell infiltration into the thyroid. Mice of the H-2 k haplotype displayed the highest incidence of severe disease, compared with 10w incidence of mild disease in mice of the b haplotype (Vladutiu and Rose 1971, Rose et al. 1981). The titers of MTg antibodies were less discriminating than histopathologic findings. Lymphocyte proliferative responses as well as the production of antibody and thyroid lesions are under H-2 control (Christadoss et al. 1978).
The principal gene controlling susceptibility to EAT, Ir-Tg, was mapped to the K and/or I-A region (Tomazic et al. 1974). At that time, suitable intra-H-2 recombinant strains were not available to permit more precise localization of the gene. Recently we have found that genes at the D end modify the severity of thyroid lesions (Kong et al. 1979). Other studies of a K-region mutant, B6.C-H-2 bin1 (H1), have suggested that a gene in this region regulates susceptibility to thyroiditis (Maron and Cohen 1979).
To distinguish the relative contribution of the K and I-A regions to EAT, several new intra-H-2 recombinant strains and H-2K-region mutants have been used to pinpoint the Ir-Tg gene. In this brief communication, we report the definitive mapping of the major Ir-Tg gene to the I-A subregion. Our intra-H-2 recombinant study further suggests that the K region, like the D region, may modify the incidence of thyroiditis. In contrast to the finding of Maron and Cohen (1979), our use of 6 K b region mutants, including bml, did not show an increased incidence of EAT.