THYROTROPIN RECEPTOR-SPECIFIC ANTIBODIES IN BALB CJ MICE WITH EXPERIMENTAL HYPERTHYROXINEMIA SHOW A RESTRICTED BINDING-SPECIFICITY AND BELONG TO THE IMMUNOGLOBULIN G1 SUBCLASS/

Immunization with the extracellular domain of TSH receptor (TSHR) led to the development of hyperthyroxinemia in BALB/cJ, but not C57BL/6J, SJL/J, and B10.BR, mice. Earlier, human studies had shown that thyroid -stimulating antibodies are predominantly of the immunoglobulin G1 (Ig G1) subclass with a narrow specificity to TSHR, and antibodies that bl ock thyroid function could be of any subclass with a broader specifici ty. Therefore, antibody responses in susceptible (BALB/cJ) and resista nt (SJL/J) mice were characterized. There were no significant differen ces in the titers, relative affinities, or isotypes of antibodies agai nst the TSHR. BALB/cJ and SJL/J sera reacted with 2 and 7 of 26 overla pping peptides from the extracellular domain of the TSHR. The ability of sera from BALB/cJ and SJL/J mice to block TSH binding to TSHR was r eversed by 1 and 6 of the reactive peptides, respectively. BALB/cJ mic e showed predominantly an IgG1 response against the TSHR and peptides, whereas SJL/J mice showed varying levels of all IgG subclasses. Altho ugh SJL/J sera reacted with peptides to which blocking antibodies bind , they did not show hypothyroidism, suggesting that their sera contain ed a mixture of blocking and stimulating antibodies that negated the e ffects of each other. In contrast, some TSHR-specific antibodies in BA LB/cJ probably represented stimulating antibodies.