Non-covalent interactions between heavy and light chains of immunoglobulin G: role of light chain variable-region subgroup

Previous studies have shown that the forward rate constants governing the non-covalent association of heavy and light chains of different IgG myeloma proteins vary considerably. In the present study rate constants, absorption difference spectra enthalpies associated with recombination have been determined using kappa chain of known variable-region subgroup specificity. The basic experimental approach was to allow a single species by γ chain to react reparately with several kappa chains belonging either to the κIII subgroup. The rate constant varied by two orders of magnitude but there was no evidence that this variability was related to subgroup specificity. There was as much variation within a subgroup as between subgroups. A correlation was noted, however, between the rate constants and the species of heavy chain used in the recombination reactions. The shape and magnitude of the difference spectra generated upon subunit association were also variable but again this could not be correlated with subgroup specificity. Variations in enthalpies of association were less striking but there were some indications that values for δH depended on the heavy chain used. Only for one of the heavy chains used was there evidence to indicate that the preferential recombination of autologous subunits observed in equilibrium systems arises because autologous subunits associate more rapidly than heterologous chains. The data presented indicate that sequence variations in either the hypervariable regions, or the framework within a subgroup, play an important role in subunit association.