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 (IgG1) subclass with a narrow specificity to TSHR, and antibodies that block thyroid function could be of any subclass with a broader specificity. Therefore, antibody responses in susceptible (BALB/cJ) and resistant (SJL/J) mice were characterized. There were no significant differences in the titers, relative affinities, or isotypes of antibodies against the TSHR. BALB/cJ and SJL/J sera reacted with 2 and 7 of 26 overlapping 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 reversed by 1 and 6 of the reactive peptides, respectively. BALB/cJ mice showed predominantly an IgG1 response against the TSHR and peptides, whereas SJL/J mice showed varying levels of all IgG subclasses. Although SJL/J sera reacted with peptides to which blocking antibodies bind, they did not show hypothyroidism, suggesting that their sera contained a mixture of blocking and stimulating antibodies that negated the effects of each other. In contrast, some TSHR-specific antibodies in BALB/cJ probably represented stimulating antibodies.
Wagle
N M
NM
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555-1019, USA.
Patibandla
S A
SA
Dallas
J S
JS
Morris
J C
JC
Prabhakar
B S
BS
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D004198:Disease Susceptibility; D005260:Female; D006981:Hyperthyroxinemia / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013961:Thyroid Gland / Q000503:physiopathology; D013972:Thyrotropin / Q000276:immunology
D000906:Antibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D010455:Peptides; D011989:Receptors, Thyrotropin; D013972:Thyrotropin