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 H chains of an IgM [immunoglobulin M] cold agglutinin, Col [from a patient with cold hemagglutinin disease], was rendered specific by solid-state adsorptions. The anti-Col idiotype bound specifically to isolated Col H (.mu.) and L (.kappa.) chains and to intact Col IgM by 3 methods: reversal of anti-idiotype inhibition of Col cold agglutinin in an automated hemagglutination-inhibition assay system; adsorption of the anti-idiotype by affinity gels consisting of Col IgM, .mu. or .kappa. chains covalently coupled to Sepharose 2B; binding of Col IgM and its isolated chains by an anti-idiotype affinity gel. Fragments of Col L chain lacking constant region determinants but still capable of inhibiting anti-idiotype were produced by limited pepsin digestion of the L chains. The finding of shared idiotypic determinants on isolated H and L 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, genes coding for hypervariable regions may be available for insertion into the DNA for H and L chains.