Monoclonal antibodies to hepatitis B surface antigen (HBsAg) with anti-alpha specificity recognize a synthetic peptide analogue (S135-155) with unmodified lysine (141).

A synthetic peptide corresponding to residues 135-155 (S135-155) of the major protein component of HBsAg was conjugated to beta-galactosidase. This conjugate reacted with monoclonal anti-HBs antibodies having anti-alpha group specificity. The reaction was inhibited by: HBsAg of either subtype ad or ay; by unconjugated S135-155 or a shorter peptide S140-155, but not by unrelated peptides. Modification of lysine residues of either HBsAg or S135-155 reduced this inhibitory effect. These results indicate that Lys 141 is essential for maintaining the antigenicity of one of the epitopes responsible for the common alpha specificity of HBsAg and that studies involving the use of synthetic peptides and modifications of distinct amino acid residues in the native protein or in the peptide may help in characterizing epitopes of viral antigens in general.