INTERACTION OF THYROID-HORMONES WITH IMMUNOGLOBULINS FROM HUMAN BLOOD-SERUM .1. PARAMETERS OF COMPLEX-FORMATION AND THE NATURE OF THE BINDING REACTION

Kinetic and equilibrium parameters characterizing thyroxine (T-4) interactions with immunoglobulins (Igs) A, G, and M and the Bence-Jones proteins isolated from human blood serum have been studied. Complex formation was time-dependent, reversible, saturable, and sensitive to specific inhibitors. The L(ae)- and L(lambda)-chains of Igs appeared to be both necessary and sufficient for T-4 binding. Covalent attachment of an H-chain either produced a sharp increase in Ig affinity for T-4 (IgM mu-chain) or altered the sensitivity of the binding site to chemical agents and pH of the medium (IgM mu-chain, Ige gamma-chain). Our data showed that the T-4-binding IgM was distinct from pathological autoantibodies against T-4 First, effects of physical and chemical factors of the medium on T-4 binding by IgM were the same as those reported for interactions of ordinary transport proteins with thyroid hormones. Second, the detection frequency of the T-4-binding IgM in randomly collected serum samples of healthy individuals was 100%. Third, the T-4-IgM complex was structurally distinct from antigen-antibody complexes since it failed to bind the first complement component (C1q). Conventionally used methods of analysis failed to detect the weak T-4-binding activity in physiological fluids containing an endogenous binding inhibitor (Cl-). Addition of exogenous inhibitors (8-anilino-1-naphthalenesulfonate) probably made the detection even more problematic. It is tempting to speculate that the discovery of specific T-4-binding properties of normal serum Igs might be hampered by lack of appropriate methodology.