Structural and functional studies on a unique linear neutralizing antigenic site (G5) of the rabies virus glycoprotein.
The core of a unique linear neutralization epitope (G5) on the glycoprotein of rabies virus, recognized by a virus-neutralizing mouse monoclonal antibody (MAb 6-15C4), was determined by Pepscan analysis. The G5 epitope was defined as an octapeptide (LHDFRSDE). The contribution of the individual amino acids of the G5 epitope to the binding of MAb 6-15C4 was analysed with a set of synthetic peptides in which the individual amino acids had been replaced in turn by each of the other 19 naturally occurring amino acids. Five amino acids of the octapeptide proved to be essential for the binding of MAb 6-15C4. The conservation of the G5 epitope within the glycoprotein of the different rabies virus strains sequenced to date proved to be absolute at the amino acid level. Studies concerning the immunodominance of the G5 epitope were carried out by determining the presence of G5 epitope-specific serum antibodies in vaccinated human and mice, and by determining the frequency of G5 epitope-specific B lymphocytes in the blood of vaccinated humans. These studies indicated that antibodies to the G5 epitope constitute a minor population of the rabies virus-specific serum antibodies induced by rabies vaccination.
van der Heijden
R W
RW
Laboratory of Immunobiology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Langedijk
J P
JP
Groen
J
J
UytdeHaag
F G
FG
Meloen
R H
RH
Osterhaus
A D
AD
D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D017124:Conserved Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011819:Rabies Vaccines / Q000276:immunology; D011820:Rabies virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D011819:Rabies Vaccines; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus