Nonoverlapping T and B cell determinants on an hepatitis B surface antigen pre-S(2) region synthetic peptide.
We have examined T cell recognition of a hepatitis B surface antigen (HBsAg), pre-S(2)-region synthetic peptide, p120-145, in terms of fine specificity, H-2-linked genetic influences, comparison to antibody binding, and relevance to T cell recognition of the native protein. We showed that the immune response to the synthetic peptide is regulated by H-2-linked genes, but that the pattern of H-2 restriction differed from that observed for the native anti-pre-S(2) response. Dominant and nonoverlapping T cell and B cell recognition sites were identified on the synthetic peptide p120-145. T cell recognition is focussed on the NH2-terminal sequence, and antibody (B cell) recognition is focussed on the COOH-terminal sequence. The fine specificity of T cell recognition of p120-145 was defined by a single, subtype-dependent amino acid substitution. With respect to the immunogenicity of p120-145, the synthetic peptide containing both T and B cell determinants is highly immunogenic in responder strains, whereas separate T or B cell peptide determinants are minimally immunogenic. Furthermore, the synthetic T cell recognition site can prime T cell help for antibody production to the synthetic B cell site, which is crossreactive with the native pre-S(2) region of HBsAg/p33 particles. This system provides evidence that totally synthetic T cell and B cell recognition sites can be combined to yield a functional immunogen.
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D000939:Epitopes; D006183:H-2 Antigens; D006514:Hepatitis B Surface Antigens; D010446:Peptide Fragments; D014764:Viral Proteins