Identification of a new group-specific determinant on hepatitis B surface antigen with a synthetic peptide.
In a recent study we demonstrated that a synthetic peptide representing residues 124-147 of the major protein of hepatitis B surface Ag (HBsAg) undergoes spontaneous oligomerization to reconstruct one or more conformational group-specific determinants on HBsAg. The present study was undertaken to identify and characterize the HBsAg-related antigenic determinants on this oligomeric peptide (peptide OS[124-147]). A panel of nine analogs of this peptide was generated by either deleting, substituting, or chemical side chain modification of specific amino acid residues. With HBsAg subtype-specific antisera a single "a" epitope was identified as one that includes Met133 and Lys141. In addition a "d" epitope toward the amino-terminal end of the sequence was also observed. Perturbation of certain amino acid residues was found to enhance a antigenicity and subsequent experiments indicated that maximal expression of this a antigenicity is dependent in part on accessibility of the Lys141 side chain and in part on the primary sequence. With a total of 50 human anti-HBsAg serum samples obtained from individuals vaccinated against hepatitis B, it was demonstrated that these sera recognize the Met133-Lys141-dependent a epitope as the dominant, and in many cases the only, determinant on peptide OS[124-147]. Finally, on immunization, peptide OS[124-147] elicits an anti-HBsAg response that is predominantly anti-a though a lesser contribution from an anti-d response was also obtained.
Manivel
V
V
International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Panda
S K
SK
Rao
K V
KV
D000595:Amino Acid Sequence; D000939:Epitopes; D006508:Hepatitis Antibodies / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008715:Methionine / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship
D000939:Epitopes; D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens; D010455:Peptides; D008715:Methionine; D008239:Lysine