Abstract
The immediate precursors of antibody molecules, the heavy (H) and light (L) peptide chains of the immunoglobulins, combine with each other by means of disulfide bonds formed by dehydrogenation of their cysteine residues. In the absence of an antigen this process yields the heterogeneous mixture of normal immunoglobulins. Antigens or their processed derivatives (Ag) interfere with this stochastic process by noncovalent combination with complementarily fitting H chains. The (Ag.H)(n) complexes thus formed, owing to the loss of rotational and translational freedom, combine preferentially with those L chains whose V(L) regions have some affinity for the determinants of the antigen molecule. Subsequent release of Ag from the (Ag.H.L)(n) complexes yields free antigen and antibody molecules. Each of the released Ag molecules can be used repeatedly for the same reaction cycle and thus can induce the biosynthesis of a large number of antibody molecules. Any macromolecule, natural or synthetic, that has at least a few polar groups and that can penetrate to the nascent H and L chains can thus act as an antigen. Whereas the structure of the H and L chains is genetically determined and transmitted through the germ line, the process induced by the antigen is a phenotypic phenomenon. The antigen acts in this process as a stereospecific cofactor or regulator of the thiol-disulfide transhydrogenation of the combining H and L chains of immunoglobulins.