Relationship between the Papain Sensitivity of Human γG Immunoglobulins and their Heavy Chain Subclass

Abstract

WE have described the recognition of two conformational forms of γG immunoglobulin, distinguished by their differing susceptibility to proteolysis by papain in the absence of cysteine^1,2. Myeloma γG globulins from different individuals were similarly characterized as sensitive or resistant to papain cleavage in these conditions. We report now (a) the results of papain sensitivity studies on myeloma proteins of the four known γG chain sub-classes; (b) the immunological relationship between the papain sensitive and resistant forms of normal γG immunoglobulin and these myeloma proteins; and (c) the carbohydrate composition of myeloma proteins of each sub-class. These studies show that it is only the γG1 and γG3 sub-class population of normal γG immunoglobulin which undergo papain proteolysis in the absence of cysteine. Susceptibility to cleavage by papain can thus be used for the preliminary assignment of myeloma proteins to the γG1, γG3, or γG2, γG4, sub-classes. Furthermore, γG2 and γG4 myeloma proteins can be distinguished from each other by their behaviour on incubation with papain in the presence of cysteine (at 37° C, for 4 h). Proteins of the latter sub-class are completely digested to Fab and Fc fragments in these conditions, whereas those of the former undergo only 10–20 per cent digestion.