Molecular Mimicry of Hepatitis B Surface Antigen by an Anti-Idiotype-Derived Synthetic Peptide

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 24; pp. 11900 - 11904
• Main Authors: Pride, Michael W., Shi, Hong, Anchin, Jerry M., Linthicum, D. Scott, LoVerde, Philip T., Thakur, Arvind, Thanavala, Yasmin
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.12.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Sequence; Amino acids; Animals; Antibodies; Antibodies, Anti-Idiotypic - chemistry; Antibodies, Anti-Idiotypic - immunology; Antibodies, immunoglobulins; Antigens; Base Sequence; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Epitopes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hepatitis; Hepatitis antigens; Hepatitis B; Hepatitis B Surface Antigens - chemistry; Hepatitis B Surface Antigens - immunology; Hepatitis B virus; Humans; Immunology; In Vitro Techniques; Infections; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Molecular immunology; Molecular Sequence Data; Monoclonal antibodies; Oligodeoxyribonucleotides - chemistry; Peptides - chemistry; Peptides - immunology; T lymphocytes; Vaccination; Human; Hepatitis B surface antigen; Immune response; Antigenic determinant; Peptides; heavy-Peptide chain; Variable region; Rodentia; Homology; Stimulation; Monoclonal antibody; Virus; Vertebrata; Mammalia; Synthetic product; Mouse; Hepadnaviridae; Antiidiotypic antibody; Hepatitis B virus; Lymphocyte
• DOI: 10.1073/pnas.89.24.11900
• ISSN: 0027-8424

Monoclonal antibody 2F10 is an "internalimage" anti-idiotype (anti-id) antibody capable of mimicking the group-specific "a" determinant of human hepatitis B surface antigen (HBsAg). By mRNA sequencing and computer-assisted molecular modeling of monoclonal antibody 2F10, we identified a 15-amino acid region of the heavy-chain hypervariable region that has partial residue homology with sequences of the "a" determinant epitopes of HBsAg. We have established that a linear 15-mer peptide from a contiguous region on the anti-id antibody can (i) generate anti-HBsAg-specific antibodies when injected into mice, (ii) prime murine lymph node cells for in vitro HBsAg-specific T-cell proliferative responses, and (iii) stimulate in vitro human CD4+T cells that were primed in vivo to HBsAg by natural infection with hepatitis B virus or vaccination with a commercially available HBsAg vaccine. Significantly, this peptide could also stimulate CD4+T cells of human hepatitis B virus carriers. We conclude that a 15-mer peptide derived from the anti-id sequence can duplicate the B- and T-cell stimulatory activity of the intact anti-id antibody and the antigen that is mimicked, HBsAg.