Antigenic regions within the hepatitis C virus envelope 1 and non‐structural proteins: identification of an IgG3‐restricted recognition site within the envelope 1 protein

SUMMARY Antibody binding to antigenic regions of hepatitis C virus (HCV) envelope 1 (El; residues 183–380), E2/non‐structural (NS) 1 (residues 380–437), NS1 (residues 643–690), and NS4(1684–1751) proteins were assayed for 50 sera with antibodies to HCV (anti‐HCV) and for 46 sera without anti‐HCV. Thirty‐four peptides. 18 residues long with an eight‐amino acid overIap within each HCV region, were synthesized and tested with all 96 sera. Within the E region 183–380, the major binding site was located to residues 203–220, and was recognized by eight sera. Within the E2/NS1 region 380–437, the peptide covering residues 410–427 was recognized by two sera, and within the NSl region 643–690, peptides covering residues 663–690 were recognized by four sera. Within the NS4 region 1684–1751, 27 sera were reactive to one or more of the NS4 peptides, and 21 out of these were reactive with peptide 1694–1711. One part of the major binding site could be located to residues 1701–1704, with the sequence Leu‐Tyr‐Arg‐Glu. The IgGl, IgG3 and IgG4 subcIasses were reactive with the five antigenic regions of HCV core, residues 1–18, 11–28, 21–38, 51–68 and 101–118. Reactivity to the major envelope site consisted almost exclusively of IgG3, and reactivity to the major site of NS4 consisted only of IgG1. Thus, a non‐restricted IgG response to linear HCV‐encoded binding sites was found to the core protein, whereas IgG subcIass‐restricted linear binding sites were found within the El protein, and within the NS4 protein.