Exposure of thyroxine residues in human thyroglobulin. Two-site binding studies

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Abstract
Human thyroglobulin (Tg) could be adsorbed through 1 of its thyroxine (T4) residues by either of 2 T4-binding antibodies which had been covalently attached to Sepharose-CL4B. The antibodies used were a purified human autoantibody specific for a T4-containing epitope in human Tg, or a rabbit antibody raised against T4 conjugated to bovine albumin side chains. Tg adsorbed by either immobilized antibody could then itself adsorb either type of antibody free in solution on to a further T4 residue. At least 2 T4 residues in human Tg are, therefore, sufficiently exposed to interact with T4-binding antibodies. Furthermore, these T4 residues are sufficiently far apart to allow the binding of 2 Ig molecules simultaneously. Previous observations of a marked preference by human autoantibodies for 1 of the T4-containing epitopes in Tg, therefore, reflect a higher binding energy with that epitope rather than an inability to interact with other''s. The T4-containing epitope which preferentially reacts with human Tg autoantibodies must, therefore, have a distinctive topography.