title: Immune responses to the hepatitis C virus NS4A protein are profoundly influenced by the combination of the viral genotype and the host major histocompatibility complex.
abstract: The interaction between the host major histocompatibility complex (MHC) and the genotype of the hepatitis C virus (HCV) was analysed using synthetic full-length non-structural (NS) 4A proteins, residues 1658-1712, of genotypes 1b, 2b, 3a, 4a and 5a. Human and murine antibodies specific for the five NS4A genotypes analysed focused on residues 1688-1707. In immunized B10 H-2 congenic mice, the H-2d, H-2f and H-2s haplotypes were good responders to NS4A, irrespective of the viral genotype. In contrast, the H-2k haplotype was a low or non-responder to all NS4A genotypes, except for genotype 2b. Also, H-2f- and H-2s-restricted NS4A genotype 1b-specific T-cells focused on residues 1670-1679 and 1683-1692, respectively, whereas H-2k-restricted NS4A genotype 2b-specific T-cells focused on the carboxy terminus. Interestingly, H-2f-restricted genotype 1b-specific T-cells did not cross-react with T-cell site analogues of seven other genotypes, whereas the H-2s-restricted, genotype 1b-specific T-cells cross-reacted with genotypes 1a, 4a and 5a. Thus the combination of viral genotype and host MHC profoundly influences the ability to mount an HCV NS4A-specific immune response.
authors.affiliation: Division of Clinical Virology, Huddinge University Hospital, Sweden.
authors.forename: Z X
authors.initials: ZX
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Hultgren
authors.forename: A
authors.initials: A
authors.lastname: Birkett
authors.forename: D R
authors.initials: DR
authors.lastname: Milich
authors.forename: M
authors.initials: M
authors.lastname: Sällberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007109:Immunity; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; C093542:NS4 protein, hepatitis C virus; D017361:Viral Nonstructural Proteins