Hepatitis delta antigen. Antigenic structure and humoral immune response.
Hepatitis delta virus (HDV) is a small RNA virus that is dependent on helper functions provided by hepatitis B virus. The hepatitis delta Ag (HDAg) is the only protein known to be made from the viral genome, from an ORF with a coding capacity of 214 amino acids. The immunogenic epitopes of HDAg and the immune response to it were mapped by the use of synthetic peptides, antipeptide antibodies, and human mAb. Antipeptide sera covering approximately 60% of the linear sequence reacted with liver-derived HDAg. Antisera from HDV-infected humans, chimpanzees, and woodchucks reacted with from 2 to 13 of 15 peptides. The epitopes of two human anti-HD mAb were mapped to overlapping but distinct epitopes in the region around residues 106-123. Sera from infected humans, chimpanzees, and woodchucks were also tested by competition with the mAb. Use of the peptides and antipeptide sera defined one region in the sequence (residues 52-93) which is immunodominant in the immune response to HDAg. Reactivity of both peptides and antipeptide antibodies was very broad, covering most or all of the linear sequence. Competition assays also provided information on conformational epitopes, as well as the sequential epitopes defined by direct assays. The peptides and antipeptide antibodies should be useful in new assay development, in dissecting the anti-HD response in terms of chronic vs self-limited infection, and in studying the role of anti-HD in infection and recovery.
Bergmann
K F
KF
Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, MD 20852.
Cote
P J
PJ
Moriarty
A
A
Gerin
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D000956:Antigens, Viral / Q000276:immunology / Q000302:isolation & purification; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D000939:Epitopes / Q000032:analysis; D006508:Hepatitis Antibodies / Q000096:biosynthesis* / Q000276:immunology; D003699:Hepatitis D / Q000276:immunology; D035923:Hepatitis delta Antigens; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008392:Marmota; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D006508:Hepatitis Antibodies; D035923:Hepatitis delta Antigens; D007106:Immune Sera; D010455:Peptides; C442244:hepatitis delta virus large antigen