Through the use of absorbed idiotypic antisera prepared against single isolated monoclonal IgM anti-γ-globulins, partial cross-idiotypic specificity was demonstrated with other IgM anti-γ-globulins. Such antisera classified these proteins into at least three groups. The major group which included 60% of the anti-γ-globulins was particularly homogeneous. The anti-γ-globulin specific antigens were detected best in hemagglutination and hemagglutination inhibition systems. They were not found in monoclonal IgM proteins that lacked anti-γ-globulin activity although related antigens were detected at low concentrations in pooled immunoglobulin preparations as well as in heterogeneous anti-Rh antibodies. Several lines of evidence were obtained indicating that the antibody combining site was involved in the specific determinants. Attempts were made to analyze the fine specificity of each anti-γ-globulin for the Fc fragment of different subclasses of human immunoglobulins as well as those of other species. Differences were observed but these were not readily related to the cross-specificity antigens. The anti-γ-globulin specific antigens were very analogous to those previously described for monoclonal IgM cold agglutinins. Although each protein could be distinguished from all the others on the basis of individual idiotypic antigens, the antigens common to the specific groups of proteins with each of these activities were prominent and readily detected with multiple antisera. The results indicate basic similarities between proteins of a given activity even in unrelated individuals.

Recent studies have indicated the presence of cross-idiotypic determinants among monoclonal IgM proteins possessing anti-T-globulin activity that were not found among IgM proteins lacking this activity (1). The pattern obtained was very similar to that previously described for the IgM cold agglutinins (2) with antigenic specificities in proteins from different individuals which appeared to relate to the combining specificity of these proteins toward their respective antigens. Evidence was obtained both for the cold agglutinins and the anti-T-globulins that the antigen-combining site was involved in these specificities. Through the use of the idiotypic antisera which showed crossspecificity, it was possible to delineate two entirely separate groups of anti-Tglobulins (1). One, the major Wa group, made up approximately 60 % of the anti-'y-globulins; the other, the minor Po group, included approximately 20 % of the total; a few anti-T-globulins could not be classified in either of these two groups.The relative role of the H and L chains of these proteins in the cross-specificities was not readily determined because the antigenic determinants involved required the combination of the chains for expression. However, amino acid sequence studies on the minor Po group of anti-3,-globulins demonstrated an extraordinary similarity in H chain sequence through two hypervariable regions (3) ; the L chains were quite distinct. This suggested that heavy chain similarities were primarily involved in the cross-specificity determinants of the minor Po group. The present studies were carried out to define these relationships further by both antigenic and sequence analyses with special emphasis on the major Wa group of anti-~-globulins. A marked similarity in the L chains of this group was found. Materials and MethodsThe IgM anti-T-globulins utilized in this study were the same as those described in a previous report (1). They were initially purified in most instances as cryoglobulins from sera where they appeared as monoclonal bands; a combined procedure using Pevikon electrophoresis and Sephadex columns as described previously (1) was then utilized for final isolation. All of the proteins precipitated with aggregated Fr II 3'-globulin and this was the primary method of