Central Laboratory, Shandong Provincial Hospital, Shandong University, Jinan, 250021, PR China.
Clin Immunol. 2010 Oct;137(1):139-46. doi: 10.1016/j.clim.2010.05.011.
Antiviral activity of natural killer (NK) cells is regulated partially through inhibitory and activating killer cell immunoglobulin-like receptors (KIR) interacting with human leukocyte antigen C (HLA-C) ligands. The highly polymorphic nature of HLA-C and KIR genes endows individuals with diverse HLA-C/KIR combinations, which may confer susceptibility to or protection against a certain challenge. We analyzed the genes encoding KIR receptors and HLA-C ligands and HLA-C/KIR combinations in patients with chronic hepatitis B and healthy subjects. We found that inhibitory receptor KIR2DL1 in combination with HLA-C2 ligand confers susceptibility to chronic hepatitis B (CHB), whereas inhibitory receptor KIR2DL3 or KIR2DL3 homozygote in the presence of HLA-C1C1 genotype shows protection against CHB. Our data reveal that inhibitory NK cell interactions are important in determining antiviral immunity and that distinct affinity inhibitory responses will exert different impact on the development of CHB.
自然杀伤 (NK) 细胞的抗病毒活性部分受到抑制性和激活性杀伤细胞免疫球蛋白样受体 (KIR) 与人类白细胞抗原 C (HLA-C) 配体相互作用的调节。HLA-C 和 KIR 基因的高度多态性使个体具有不同的 HLA-C/KIR 组合，这可能导致对某种挑战的易感性或保护。我们分析了慢性乙型肝炎患者和健康受试者中编码 KIR 受体和 HLA-C 配体及 HLA-C/KIR 组合的基因。我们发现，抑制性受体 KIR2DL1 与 HLA-C2 配体结合可导致慢性乙型肝炎 (CHB)，而抑制性受体 KIR2DL3 或 KIR2DL3 纯合子在 HLA-C1C1 基因型存在时可预防 CHB。我们的数据表明，抑制性 NK 细胞相互作用在决定抗病毒免疫中很重要，不同亲和力的抑制性反应对 CHB 的发展将产生不同的影响。
