Immune response to a single peptide containing an immunodominant region of hepatitis C virus core protein: the isotypes and the recognition site.
We have used one single peptide covering the 17 N-terminal amino acids of the hepatitis C virus (HCV) core protein (c) to analyse the human immune response against B-cell epitope(s) within this region. The sequence MSTNPKPQRKTKRNTNR was obtained from two sequenced HCV genomes, and the peptide was synthesized by a newly developed method. The peptide was assayed with 144 human sera which had all been assayed for antibodies to HCV (anti-HCV) using commercial assays. Forty-nine sera were found to be positive for anti-HCV using these assays; 40 of these were found to be positive with our anti-HCV IgG peptide assay. The class (IgM, IgG) and subclass (IgA1, IgG1-4) specific reactions were determined using the polyclonal and monoclonal anti-HCV peptide enzyme immunoassays. Isotypes of mainly IgG1 and IgG3, but also IgG4, IgM and IgG2, gave specific reactions with this region. Using omission peptide analogues of the region 1-18, the sequence RKTKRNTN within residues 9-16 was common to 34 out of 37 sera of which the IgG antibody binding site could be mapped. It is unusual for a single peptide assay to have such high sensitivity since B cell epitopes within a protein are often discontinuous. It seems that at least 80% of HCV infected individuals develop antibodies of various isotypes to the antigenic site RKTKRNTN, located in the N-terminal portion of the HCV core. Thus, the immune response to this peptide should be further investigated with regard to the reactive Ig isotypes developing during HCV infection.
Sällberg
M
M
Department of Virology, Karolinska Institute, Stockholm, Sweden.
Rudén
U
U
Wahren
B
B
Magnius
L O
LO
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D018936:Hepatitis C Antigens; D016056:Immunodominant Epitopes / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D018936:Hepatitis C Antigens; D016056:Immunodominant Epitopes; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus