An Attempt to Induce “Graves' Disease of the Gonads” by Immunizing Mice with the Luteinizing Hormone Receptor Provides Insight into Breaking Tolerance to Self-Antigens

Abstract

Our investigations provide insight into antibody responses to self-antigens. First, antibodies are induced to large self-antigens like mouse-TPO when membrane bound. Second, lesser amino acid homology between the immunogen and mouse protein (91% vs. 97% for the human-TSHR and rat-LHR, respectively) favors antibody induction. Finally, from previous studies demonstrating the immunogenicity of the highly glycosylated human TSHR A-subunit versus our present data for the nonimmunogenic less glycosylated rat LHR, we suggest that the extent of glycosylation contributes to breaking self-tolerance.

Review and Hypothesis: Does Graves' Disease Develop in Non-Human Great Apes?

“…Possible reasons for the very poor antibody response include differences in mouse genetic background, high amino acid homology between the rat LHR and mouse LHR (selfprotein), and glycosylation of the immunogen (16). Of note regarding the latter, glycosylation influences the antigenicity of infectious organisms such as Ebola virus (17) and simian immunodeficiency virus (18).…”

Of [hamsters] and men

“…Immunogenicity may initially arise in response to the foreign epitope, which then leads to epitope spreading, involving autoreactive T cells, or autoimmunity. Thus once immunogenicity is established, epitope spreading may lead to more serious sequelae 28 , 29 …”