The effect of pepsin digestion in relation to the pre-s region on hepatitis B surface antigen-induced hypersensitivity

The role of the pre-S region of the hepatitis B surface Ag (HBsAg) particle in hypersensitivity to HBsAg was evaluated in mice. Plasma-derived or recombinant HBsAg was digested with pepsin to prepare different forms of HBsAg with or without pre-S region. Strains of mice including AKR/J (H-2^k), A.SW (H-2^S), C3H/He (H-2^k), and CBA/J (H-2^k) did not respond to the major S protein with regard to hypersensitivity. However, the pre-S-containing HBsAg overcame this nonresponsiveness. In BALB/c (H-2^d) and A/J (H-2^a) mice, the pre-S-containing HBsAg induced higher hypersensitivity than did the major S protein. The enhancement induced by the pre-S region was demonstrated to occur during the induction phase by crisscross assay using pre-S-containing HBsAg and major S protein as Ag. The patterns of hypersensitivity induced by the major S, middle S (composed of major S and pre-S₂), and large S (composed of middle S and pre-S₁ proteins) were also compared. The middle S protein induced responses of 1-h and 24-h hypersensitivities in major S nonresponder (C3H/He and CBA/J) mice, whereas the large S protein circumvented only the 1-h one. The effectiveness to stimulate hypersensitivities in vivo by HBsAg is in the following order: middle S > large S > major S. These data suggest that the pre-S region of HBsAg particle can enhance both the 1-h and 24-h hypersensitivities in the afferent phase.