The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled γ-globulin and for the localization of these determinants on the γ-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of γ-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum.
The antigenic determinants responsible for the individual specificity were localized in all cases studied solely to the Fab fragment produced by papain digestion. After reductive cleavage, three patterns of localization were observed. Individual specificity could be localized either to; (a) isolated heavy chains, (b) isolated light chains, (c) antigenic determinants present only when light and heavy chains were recombined.
After immunization with whole myeloma proteins, individual specificity was localized in part at least to the isolated heavy chain in four of six proteins studied. It was localized to the light chains in three of five type L proteins but in none of six type K proteins. In the instances where individual specificity of the myeloma protein was present on the light chains, it was shown that the Bence Jones protein from the same patient also contained the individual specificity. Immunization with isolated heavy or light chains furnished further evidence for the individual specificity of both types of chains.
These studies on myeloma proteins furnished evidence concerning the portions of the γ-globulin molecule subject to individual antigenic variation. The light chains, particularly the L type and the Fd portion of the heavy chains were primarily involved. Evidence for the importance of the quaternary structure was also obtained from the necessity in some instances for light and heavy chains to be associated in order for individual specificity to be observed. The Fc fragment of the heavy chains on the other hand showed very limited variation which was related to subgroup specificity.