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

The pepsin site, an antigenic determinant of human y-globulin uncovered by proteolytic digestion of IgG 1 by pepsin, has previously been described and characterized by Osterland, Harboe, and Kunkel (3). By using anti-Rh antibodies digested with pepsin at pH 4.1, it was found that 20% of normal sera and 57% of sera from patients with rheumatoid arthritis contained anti-y-globulin factors, primarily 7 S, which agglutinated cells coated with pepsin-digested human incomplete antibody. Of particular interest was the finding that these agglutination reactions could not be inhibited by whole y-globulin, but only by pepsin or papain digests of human y-globulin performed at pH 4.1. Under these conditions a 5 S pepsin fragment re- lated to Fab-fragment remained, whereas Fc-fragment was digested to dialyzable peptides. Fab