CHARACTERIZATION OF MINOR AND MAJOR ANTIGENIC REGIONS WITHIN THE HEPATITIS-B VIRUS NUCLEOCAPSID

Hepatitis B core antibodies (anti-HBc) appear very early during the co urse of the hepatitis B virus infection and often persist years after viral clearance. In order to characterize the immunodominant domain of the HBcAg, the human immune response against the HBV nucleocapsid (HB cAg) was analyzed by using 14 synthetic peptides. Anti-HBc antibodies were detected by an indirect enzyme-linked immunosorbent assay (ELISA) with HBc peptides. Results suggest that the anti-HBc response is hete rogeneous and directed against the whole primary structure of the HBc protein. Results also indicate that the epitopes recognized by anti-HB c antibodies can vary with the stages of the disease. In most sera fro m patients with serological evidence of acute HBV infection, anti-HBc antibodies recognized all the HBc peptides; conversely, after the acut e phase, anti-HBc antibodies recognized predominantly epitopes located within the central region of the HBc protein from residue 74 to 123. Our results suggest that the HBV core protein is made up of two antige nic regions: a major one expressing a family of immunodominant epitope s from residue 74 to 123, whereas the minor encompasses the rest of th e protein. The concept of the conformational nature of the unique HBcA g determinant is discussed, suggesting numerous families of linear epi topes. (C) 1993 Wiley-Liss, Inc.