Immunochemical, electrophoretic, and genetic heterogeneity of pepsinogen I. Characterization with monoclonal antibodies.

Two immunologic subclasses of human pepsinogen I alpha-PG I and beta-PG I, have been identified based on their reactivity toward a murine monoclonal antibody that recognizes an epitope on the alpha-PG I isozymogens. The antibody was used to purify the major alpha- and beta-isozymogens from gastric mucosa and to determine their contributions to the previously described genetic polymorphism of PG I. The alpha-epitope was localized to the pepsin region of the molecules. The two major alpha-PG I isozymogens (Pg 3 alpha and Pg 5 alpha) and the major beta-PG I isozymogen (Pg 4 beta) were demonstrated to contain net charge differences located in the respective pepsin and activation peptide regions. We propose that the alpha- and beta-subclasses contain net charge amino acid substitutions encoded by the corresponding pepsinogen genes: PGA3, PGA4, and PGA5.