Cross-reactive variable-region associated epitopes of human IgG1 lambda paraprotein detected by a monoclonal antibody...

This paper describes the production and characterization of a panel of 15 mouse monoclonal antibodies selected for putative activity against V-region related or allotypic determinants of a single IgG1 lambda paraprotein obtained from a patient with malignant lymphoplasmacytoid lymphoma. The specificity of each reagent for epitopes on the heavy (H) or light (L) chain or for conformational determinants (CD) of the immunogen was determined and the ability of one reagent to compete with another for these sites investigated. The fine specificity of the antibodies was assessed by screening on a large series of normal and paraprotein-containing sera. One monoclonal showed specificity for the Glm(f) allotype. The 14 other reagents identified a minimum of nine different epitopes in the V region of the immunogen, with four antibodies detecting private conformationally determined idiotypic specificities. Eight determinants were V-region markers also expressed on other paraproteins. A total of 30 out of 159 different paraproteins cross-reacted with one or more of the antibodies. Four of the shared epitopes were lambda-chain associated, three were H-chain associated and one was a conformational determinant. Homologies of lambda chain were identified more frequently among other paraproteins than those of H chain. The relationship between epitope expression and H-chain class of paraprotein was not random. The frequency of expression of cross-reactivities in association with IgG1 proteins was always exceeded by higher frequency of epitope expression in association with other classes of H-chain isotype. The potential therapeutic value of such panels of characterized monoclonal reagents is discussed.