Cross-reactive idiotypes on high affinity IgG class human monoclonal thyroglobulin autoantibodies

Abstract

Anti-idiotypic antibodies have been developed in rabbits against three high affinity IgG class monoclonal human autoantibodies to thyroglobulin (Tg), which resemble polyclonal Tg antibodies in patients with autoimmune thyroid disease. Antibodies to 1E10 monoclonal anti-Tg (IgG2 kappa) recognised a cross-reactive idiotype (CRI) also present on 1D3 monoclonal anti-Tg (IG1 lambda) and on VB5 monoclonal anti-Tg (IgG2 lambda). The determinant to which anti-1E10 binds appears to involve, at least in part, the binding site for Tg. In contrast, anti-idiotypic antibodies raised against VB5 failed to bind to either 1E10 or 1D3, a finding consistent with previous studies on serum polyclonal Tg antibodies, which suggested that such antibodies exhibit a mixture of private and cross-reactive idiotypes. The observed sharing of idiotypic determinants was not related to subclass, light chain type or expression of a particular VH gene family in the heavy chain. Although binding of the anti-idiotypic antibodies to Tg antibodies in a panel of patients (including the donors of the lymphocytes used to produce the monoclonal antibodies) could not be detected, the monoclonal antibodies are representative of the donor patients' serum Tg antibodies, both in terms of IgG subclass and functional affinity. Thus these idiotypes may be present in patients' sera at levels below the detection limits of the assays employed. Cross-reactive regulatory idiotypes in mice often constitute a minor component of the anti-Tg repertoire. Consequently, it is possible that low levels of a CRI, such as the 1E10 CRI, may be involved in the regulation of the autoimmune response to Tg in man.