Zhang Z X, Chen M, Hultgren C, Birkett A, Milich D R, Sällberg M
Division of Clinical Virology, Huddinge University Hospital, Sweden.
J Gen Virol. 1997 Nov;78 ( Pt 11):2735-46. doi: 10.1099/0022-1317-78-11-2735.
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.
利用1b、2b、3a、4a和5a基因型的合成全长非结构（NS）4A蛋白（第1658 - 1712位氨基酸残基），分析了宿主主要组织相容性复合体（MHC）与丙型肝炎病毒（HCV）基因型之间的相互作用。针对所分析的5种NS4A基因型的人和鼠抗体聚焦于第1688 - 1707位氨基酸残基。在免疫的B10 H - 2同源基因小鼠中，H - 2d、H - 2f和H - 2s单倍型对NS4A是良好的反应者，与病毒基因型无关。相比之下，H - 2k单倍型对除2b基因型外的所有NS4A基因型是低反应者或无反应者。此外，H - 2f限制的NS4A 1b基因型特异性T细胞分别聚焦于第1670 - 1679位氨基酸残基和第1683 - 1692位氨基酸残基，而H - 2k限制的NS4A 2b基因型特异性T细胞聚焦于羧基末端。有趣的是，H - 2f限制的1b基因型特异性T细胞不与其他7种基因型的T细胞位点类似物发生交叉反应，而H - 2s限制的1b基因型特异性T细胞与1a、4a和5a基因型发生交叉反应。因此，病毒基因型和宿主MHC的组合深刻影响了产生HCV NS4A特异性免疫反应的能力。
