Demonstration of an idiotypic antigen on a monoclonal cold agglutinin and on its isolated heavy and light chains

Abstract

A potent anti-idiotype serum produced in a rabbit immunized with the isolated heavy chains of an IgM cold agglutinin "Col" was rendered specific by solid-state adsorptions. The anit-Col idiotype was shown to bind specifically to both isolated Col heavy (mu) and light (kappa) chains as well as to intact Col IgM by three methods: (i) reversal of anti-idiotype inhibition of Col cold agglutinin in an automated hemagglutination-inhibition assay system; (ii) adsorption of the anti-idiotype by affinity gels consisting of Col IgM, mu, or kappa chains covalently coupled to Sepharose 2B; (iii) binding of Col IgM and its isolated chains by an anti-idiotype affinity gel. Fragments of Col light chain lacking constant region determinants but still capable of inhibiting anti-idiotype were produced by limited pepsin digestion of the light chains. The finding of shared idiotypic determinants on isolated heavy and light chains of a monoclonal antibody suggests that these chains share a common sequence in a hypervariable region. As an extension of the gene insertion theory of Wu and Kabat, we postulate that genes coding for hypervariable regions may be available for insertion into the DNA for both heavy and light chains.