Adjuvant effects of cholera toxin b subunit on immune response to recombinant thyrotropin receptor in mice.
We had previously shown that BALB/c mice immunized with the extracellular domain of human thyrotropin receptor (ETSHR) developed moderate hyperthyroxinemia. The antibody responses in these mice were predominantly of the IgG1 subclass. Since cholera toxin B subunit (CT-B) has direct effects on the thyroid, and is known to activate B lymphocytes and cause enhanced IgG1 production, we tested the ability of CT-B to modulate the antibody response to ETSHR. CT-B is unique in that it not only elicits a strong immune response to itself, but more importantly, when given with other antigens acts as a potent adjuvant. In the present study, BALB/c mice given ETSHR with CFA or CT-B via ip route showed higher titers of antibodies to ETSHR when compared to mice similarly immunized with ETSHR alone, or with IFA. Antibodies in ETSHR+CT-B immunized mice were mostly of the IgG1 subclass and reacted predominantly with ETSHR peptides 1 (aa 22-41), 21 (aa 322-341), and 23 (352-371). In contrast, animals immunized with ETSHR+CFA showed IgG1, IgG2a and IgG2b responses and reacted with peptides 1 and 21. Furthermore, mice immunized with ETSHR along with CT-B showed significantly higher levels of thyrotropin (TSH) binding inhibitory immunoglobulins (TBII) compared to those that did not receive CT-B. None of the mice immunized with a control antigen showed antibody response to ETSHR. These results suggested that CT-B could enhance and modulate immune response to ETSHR.
Fan
J L
JL
Department of Microbiology and Immunology, College of Medicine, The University of Illinois at Chicago, IL, 60612-7344, USA.
Peterson
J W
JW
Prabhakar
B S
BS
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015551:Autoimmunity; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D006981:Hyperthyroxinemia / Q000209:etiology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D011989:Receptors, Thyrotropin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins; D002772:Cholera Toxin