Genetic control of the murine humoral response to distinct epitopes of hepatitis C virus core protein

Recombinant hepatitis C virus (HCV) core protein from aa1-164, designated cp1-10, was used to immunize mice. Antibodies to cp1-10 were produced in all seven strains of congenic mice; none of the strains could be considered low responders relative to the others. The mouse response against individual epitopes of HCV core protein varied from one strain to another: B10.RIII (H-2r) recognized all three peptides aa13-30, aa77-90, aa129-145; B10.D2 (H-2d), B10 (H-2b) and C3H.SW (H-2b) responded to aa13-30, aa77-90; B10.M (H-2f), B10.BR (H-2k) and C3H/Hej (H-2k) reacted with aa13-30 only. Competitive inhibition of binding demonstrated that antibody to the peptide was inhibited by cp1-10 protein and the corresponding peptide only. Recombinant HCV core protein is highly immunogenic and can elicit good antibody response in mice. The aa13-30 is a major epitope of HCV core protein in mice. The humoral response to the distinct epitopes was regulated by the H-2 genes. Further analysis indicated that the I-a locus of H-2 genes determined the antibody response to aa13-30 and 77-90. These results suggest that the variation of antibody responses to HCV in humans may partially contribute to different outcomes of HCV infection.