Regulation of autoimmune response to mouse thyroglobulin: influence of H-2D-end genes.

Studies were initiated to define the H-2-linked genetic control of response to self-determinants of MTg. In addition to the Ir gene control of H-2K end, a modifying effect of D end was seen. The extent of regulation depended upon the derivation of the K-end Ir-Tg gene(s) as well as the D-end genes. When the Ir-Tg gene was from good responder H-2k and H-Ss strains, and the H-2D-end gene from the d allele, antibody levels were moderate to high but cellular infiltration was significantly reduced. These findings demonstrate genetic interaction between I-region and D-end gene products in the response to a self-antigen, MTg.

Syngeneic thyroglobulin is immunogenic in good responder mice.

Mouse thyroglobulin (MTg) or thyroid extract (TE) was given repeatedly to good responder C3H/Anf (H-2k) and poor responder BALB/c (H-2d) mice in the absence of adjuvant. Anti-MTg antibodies reached high levels in good responder mice given high doses of thyroid antigen. To eliminate stimulation by alloantigenic determinants and reduce the chance of denaturation. TE from syngeneic mice was prepared freshly each week and injected into good and poor responder strains. Again, significant antibody titers were observed in good responder mice. The antibody was specific for MTg since (a) it was not inhibited by extracts of other organs and (b) it reacted strongly with the closely related rat Tg and weakly with Tg from other species. Histology revealed mononuclear cell infiltration of the thyroid of good responder, but not of poor responder mice, regardless of the strain used to provide the thyroid antigen. The data demonstrate the presence of both T and B cell populations reactive with this self antigen and their stimulation by repeated high doses of antigen, without the aid of adjuvant, to override the regulatory controls that normally prevent autoimmune responses.