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Human Monoclonal Thyroglobulin Autoantibodies of High Affinity. II. Interaction Between Thyroglobulin and Thyroglobulin Autoantibodies of Different IgG Subclasses
N. Fukuma, Sandra M. McLachlan, Masateru Horimoto, Vaughan B. Petersen, Bernard Rees Smith
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Abstract
The interaction of human thyroglobulin (Tg) autoantibodies of different IgG subclasses with Tg was investigated using four high affinity human monoclonal thyroglobulin (Tg) autoantibodies, secreted by human-mouse hybridomas, of subclasses IgGl (kappa and lambda) and IgG2 (kappa and lambda) and an IgG4 kappa serum monoclonal Tg antibody. With exception of a low level of interference in binding between one IgGl lambda Tg antibody and one IgG2 kappa Tg antibody (27% decrease), binding by human monoclonal Tg antibodies of one IgG subclass was unaffected by pre-incubation of 125-1 Tg (or Tg on an ELISA plate) with a human monoclonal Tg antibody of a different IgG subclass. Furthermore, preincubation of Tg-coated ELISA plates with an IgGl human monoclonal Tg antibody had little effect on binding to Tg by IgG2, IgG3 and IgG4 Tg antibodies present in the sera of 6 Hashimoto patients. Comparable observations were made using an IgG2 monoclonal Tg antibody and serum Tg antibodies of subclasses IgGl, IgG3 and IgG4. Binding of an IgGl kappa Tg antibody was inhibited (>80%) by pre-incubation of Tg with an IgGl lambda Tg antibody derived by fusion of lymphocytes from the same Hashimoto patient. In contrast, pre-incubation of Tg with an IgG2 kappa Tg antibody had little effect on subsequent binding by an IgG2 lambda Tg antibody derived from lymphocytes of a different Hashimoto patient. Overall, these observations, together with results from others showing that Tg autoantibodies present in the sera of Hashimoto patients interact with a limited number of epitopes on Tg (2-3 on each of the two identical subunits of the molecule), support our hypothesis that Tg antibodies of different IgG subclasses interact with different regions on Tg. However, it seems likely that the regions with which Tg antibodies of different IgG subclasses interact may differ slightly in individual patients.