Hapten-induced allosteric transition in the light chain dimer of an immunoglobulin

Abstract

THE dimer of immunoglobulin light chains (L₂) was shown by X-ray crystallography to be structurally homologous to the native immunoglobulin Fab fragment (HL) (refs 1–3). This led to the suggestion that L₂ is a model for a primitive antibody¹ and for the T-cell receptor^22,23. In L₂ 315 (from the mouse myeloma protein MOPC 215) functional homology was also implicated in that both L₂ and HL bind the same nitroaromatic haptens with similar fine specificity^4,5. We have considered the possibility that this homology extends also to hapten-induced conformational changes and that studies with L₂ will yield information on the nature of such processes in immunoglobulins. L₂ 315 constitutes a particularly good model system for such studies as it binds two hapten molecules per dimer at symmetry-related sites^4,5. It is thus possible to monitor the conformational effects of the first binding hapten through the mode of interaction with the second, as revealed by the shape of the saturation curve⁶. We report here that dinitrophenyl-lysine (DNPL) and its fluorescent analogue nitrobenzoxadiazole-alanine (NBDA) (ref. 7) both display sigmoidal binding curves, implying positive cooperativity in their interaction with L₂ 315. This observed cooperativity is shown to arise from a hapten-induced conformational transition which may be described by the allosteric model⁶. We propose that this allosteric transition involves changes in the relative position of the chains in L₂, lending support to suggestions^8,9 that a similar process occurs in the structurally homologous intact immunoglobulin. These findings are, therefore, relevant to the question of antigen-triggered effector functions of antibodies through an allosteric mechanism^8,10–12.