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 d omain of human thyrotropin receptor (ETSHR) developed moderate hyperthyroxi nemia. The antibody responses in these mice were predominantly of the IgG1 subclass. Since cholera toxin B subunit (CT-B) has direct effects on the th yroid, and is known to activate B lymphocytes and cause enhanced IgG1 produ ction, we tested the ability of CT-B to modulate the antibody response to E TSHR. CT-B is unique in that it not only elicits a strong immune response t o itself, but more importantly, when given with other antigens acts as a po tent 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 t o mice similarly immunized with ETSHR alone, or with IFA. Antibodies in ETS HR+CT-B immunized mice were mostly of the IgG1 subclass and reacted predomi nantly 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 thyrotropi n (TSH) binding inhibitory immunoglobulins (TBII) compared to those that di d not receive CT-B. None of the mice immunized with a control antigen showe d antibody response to ETSHR. These results suggested that CT-B could enhan ce and modulate immune response to ETSHR. (C) 2000 Academic Press.