HIV 特异性抗体依赖细胞细胞毒性 (ADCC) 压力下的免疫逃逸。
Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure.
机构信息
Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia.
出版信息
Proc Natl Acad Sci U S A. 2011 May 3;108(18):7505-10. doi: 10.1073/pnas.1016048108. Epub 2011 Apr 18.
Abstract
Effective immunity to HIV is poorly understood. In particular, a role for antibody-dependent cellular cytotoxicity (ADCC) in controlling HIV is controversial. We hypothesized that significant pressure from HIV-specific ADCC would result in immune-escape variants. A series of ADCC epitopes in HIV-infected subjects to specific consensus strain HIV peptides were mapped using a flow cytometric assay for natural killer cell activation. We then compared the ADCC responses to the same peptide epitope derived from the concurrent HIV sequence(s) expressed in circulating virus. In 9 of 13 epitopes studied, ADCC antibodies were unable to recognize the concurrent HIV sequence. Our studies suggest ADCC responses apply significant immune pressure on the virus. This result has implications for the induction of ADCC responses by HIV vaccines.
摘要
艾滋病毒的有效免疫机制尚未完全明了。特别是，抗体依赖性细胞细胞毒性 (ADCC) 在控制 HIV 方面的作用存在争议。我们假设，HIV 特异性 ADCC 会产生大量免疫逃逸变异。我们使用流式细胞术检测自然杀伤细胞激活来检测 HIV 感染者对特定共识株 HIV 肽的一系列 ADCC 表位。然后，我们比较了对来自循环病毒中表达的同一肽表位的 ADCC 反应。在所研究的 13 个表位中的 9 个中，ADCC 抗体无法识别同时存在的 HIV 序列。我们的研究表明，ADCC 反应对病毒施加了巨大的免疫压力。这一结果对 HIV 疫苗诱导 ADCC 反应具有重要意义。
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