Department of Medicine II, University of Freiburg, Germany.
Centre of Chronic Immunodeficiency (CCI), University of Freiburg, Germany.
Hepatology. 2010 Jan;51(1):54-62. doi: 10.1002/hep.23275.
Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role has been described, with the corresponding region in genotype 3 that differs in its sequence by three amino acid residues. The genotype 3a peptide was not recognized by CD8+ T cells specific for the genotype 1 peptide. Furthermore, patients with acute or chronic infection with HCV genotype 3a did not mount T-cell responses to this epitope region, and their autologous viral sequences showed no evidence of T-cell pressure. Finally, we found a significantly higher frequency of HLA-B27 positivity in patients with chronic HCV genotype 3a infection compared to genotype 1 infection, indicating that there is no protection by HLA-B27 in HCV genotype 3 infection.
Our data indicate that the protective effect of HLA-B27 is limited to HCV genotype 1 infection and does not expand to other genotypes such as genotype 3a. This can most likely be explained by intergenotype sequence diversity leading to the loss of the immunodominant HLA-B27 epitope in viral strains other than genotype 1. Our results underline the central role of a single HLA-B27-restricted epitope-specific CD8+ T-cell response in mediating protection in HCV genotype 1 infection.
人类白细胞抗原 B27（HLA-B27）与人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）感染有关。这种保护作用与这两种感染中单一免疫优势 HLA-B27 限制性 CD8+ T 细胞表位有关。为了确定特定 HLA-B27 限制性表位对 HCV 感染自然病程的相对贡献，我们比较了高度保守的 HCV 基因型 1 表位的生物学影响，该表位的保护作用已被描述，以及在序列上有三个氨基酸差异的基因型 3 的相应区域。基因型 3a 肽不能被针对基因型 1 肽的 CD8+ T 细胞识别。此外，急性或慢性 HCV 基因型 3a 感染的患者未对该表位区域产生 T 细胞反应，其自身的病毒序列没有 T 细胞压力的证据。最后，我们发现慢性 HCV 基因型 3a 感染患者中 HLA-B27 阳性的频率明显高于基因型 1 感染患者，表明 HLA-B27 在 HCV 基因型 3 感染中没有保护作用。
我们的数据表明，HLA-B27 的保护作用仅限于 HCV 基因型 1 感染，而不能扩展到其他基因型，如基因型 3a。这最有可能是由于基因型间序列多样性导致除基因型 1 以外的病毒株中丢失免疫优势 HLA-B27 表位。我们的结果强调了单一 HLA-B27 限制性表位特异性 CD8+ T 细胞反应在介导 HCV 基因型 1 感染中的核心作用。
