A common idiotype on human macroglobulins with anti-I and anti-i specificity.
The reactions of an idiotypic antiserum prepared against an anti-I cold agglutinin (Da) were studied in radioimmunoassays which were designed to detect partial rather than complete idiotypic cross-reactions among cold agglutinins with anti-I and anti-i activity. Proteins showing strong idiotypic cross-reactions by gel precipitation could not inhibit the binding of 125I-labelled Da to anti-Da (individual specificity). It was necessary to use 125I-labelled cross-reactive proteins in order to demonstrate cross-idiotypic specificity and even the choice of the reference cross-reactive protein was important. The use of the 125I-labelled Fab fragment of a cross-reactive anti-I cold agglutinin (Low) allowed the detection of an idiotypic determinant common to at least 73% of cold agglutinins with specificity for the I-i antigen complex. Among these were two transiently occurring cold agglutinins following M. pneumoniae infection and infectious mononucleosis. This idiotypic determinant was not detected on cold agglutinins with anti-Pr specificity or on isolated monoclonal IgM or IgG lacking cold agglutinin activity, but it was present in low concentrations in pooled IgG. The common idiotypic determinant was found on IgM kappa cold agglutinins belonging to different VK subgroups and on an IgM lambda protein. A knowledge of the structural basis of such idiotypic cross-reactions among proteins from unrelated individuals should provide important information about the genes controlling the synthesis of site-related regions of antibodies.