Variations among gamma-globulins at the antigenic site revealed by pepsin digestion.

Abstract

The burled antigenic determinant uncovered by pepsin proteolytic digestion of 7S [gamma] -globulin at pH 4.1 was studied in 56 isolated IgG myeloma proteins. Eighteen of the pepsin-digested M-components (Isolated monoclonal myeloma proteins) were deficient in inhibition of agglutination systems comprised by 7S human agglutinators and cells coated with pepsin-digested incomplete antibody. All pepsin-digested myeloma proteins that showed deficiency were of the Ge or Ne H-chain subgroups, with the exception of one that was typed as Vi and one that did not fall into any of the major H-chain subgroups. Pepsin-digested IgA myelomas lacked the ability to inhibit in the pepsin site system. Relationship of the pepsin site antigen to disulfide bonds was shown by loss of inhibitory capacity of both 5S pepsin-digested [gamma] -globulin or pepsin fragments of individual myelomas by progressive reduction with mercaptoethanol. Antigenic structures present on the 5S pepsin fragment but not shared by the 3.5S Fab-fragment obtained with papain digestion were detected by antisera to pepsin-digested human [gamma] -globulin with Fab-fragment produced by papain. Such antisera showed weak or incomplete precipitin reactions with pepsin-digested myelomas previously shown to be deficient in inhibition reactions. The pepsin site antigenic structure thus appears to reside on the Fd portion of [gamma] -globulin.