Importance of subtype in the immune response to the pre-S(2) region of the hepatitis B surface antigen. II. Synthetic Pre-S(2) immunogen.
One purpose of this study was to examine the influence of viral subtype on in vivo antibody production to the pre-S(2) region of the hepatitis B surface Ag. Immunization with hepatitis B surface Ag particles containing the pre-S(2) region of the d or y subtypes identified the B10.M (H-2f) strain as an antibody nonresponder to the pre-S(2) and S regions after immunization with the y subtype, but as an antibody responder to the pre-S(2) and S regions after immunization with the d subtype. Both the S region and pre-S(2) region-specific antibody responses emanated from pre-S(2)/d-specific Th cell function because B10.M mice are T cell nonresponsive to the S region of both subtypes. Although responder/nonresponder status of the B10.M strain was dependent on the pre-S(2) subtype used for immunization, the anti-pre-S(2) antibody produced was totally cross-reactive on both subtypes. This is consistent with the conserved nature of the dominant pre-S(2) antibody-binding site and the highly polymorphic nature of the pre-S(2) sequence that represents the focus of T cell recognition. These data suggest that, to fully benefit from the inclusion of pre-S(2) region sequences, third generation hepatitis B virus vaccines should contain both the d and y subtype sequences of the pre-S(2) region to increase the frequency of pre-S(2) and S-specific antibody responses and to insure Th cell memory relevant to both viral subtypes. A second purpose of this study was to "design" a synthetic pre-S(2) immunogen based on combining the dominant B and T cell recognition sites into a single peptide. A composite peptide consisting of the dominant T cell recognition sequence p151-174 positioned N-terminal to the dominant B cell site p133-143 (i.e., p151-174(133-143] yielded an effective pre-S(2) synthetic immunogen. Interestingly, the orientation of the T and B cell determinants and the context of the T cell site within the larger composite peptide influenced both antibody fine specificity and T cell fine specificity.
Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
D R
DR
Milich
J E
JE
Jones
A
A
McLachlan
G
G
Bitter
A
A
Moriarty
J L
JL
Hughes
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000939:Epitopes; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000145:classification* / Q000276:immunology; D007156:Immunologic Memory; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology / Q000648:ultrastructure
D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D010455:Peptides; D011498:Protein Precursors; D014759:Viral Envelope Proteins; C050807:presurface protein 2, hepatitis B surface antigen