Gene(s) at I-A subregion controls the autoimmune response to thyroglobulin in mice

Immunization of mice with thyroglobulin emulsified in Freund's complete adjuvant produces autoimmune thyroiditis, characterized by antibodies to thyroglobulin and infiltration of the thyroid with mononuclear cells. Some strains of mice are low and others are high responders to thyroglobulin. The immune response as reflected especially in the magnitude of the thyroid infiltration, is controlled by gene(s) within the H-2 locus. Previous attempts to map the Ir gene(s) for thyroglobulin (Ir-Tg) showed that it could be assigned to either the K or I-A subregion of H-2. An H-2 recombinant strain of mice, B10.MBR (H-2bq1), in which the H-2K is derived from the H-2b haplotype and which carries the I-Ak allele(s), was immunized with thyroglobulin. B10.MBR mice were high responders to thyroglobulin in contrast to C57BL/6 mice, which have both the H-2K and I-A from the H-2b haplotype and were low responders. This suggests that Ir-Tg, which controls the severity of autoimmune thyroiditis, maps within the I-A subregion, similar to gene(s) controlling the susceptibility to experimental myasthenia gravis.