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Cross idiotypic specificity among cold agglutinins in relation to combining activity for blood group-related antigens.

The previous observations of cross idiotypic specificity of IgM cold agglutinins were further investigated in quantitative precipitin assays and attempts were made to relate shared idiotypic specificity to combining specificity for I, i and Pr antigens of red cells. Shared idiotypic determinants were observed among anti-I and anti-i antibodies which are now known to have combining specificity for determinants present on precursors of the ABH and Lewis blood group substances. There was evidence that one cold agglutinin, Ma, which had previously been shown to have an unusual kind of I specificity was deficient in the idiotypic determinants associated with the other anti-I proteins. 
 
Anti-Pr cold agglutinins, which have specificities unrelated to I-i antigens, were found to have distinct cross idiotypic determinants which were not detected on anti-I and anti-i antibodies. IgA and IgM antibodies with Pr specificity isolated from different individuals were found to share idiotypic determinants. 
 
Cross specificity antigens were detected at low concentrations in preparations of normal IgG and IgM, but not in any isolated monoclonal macroglobulins lacking cold agglutinin activity.