Smith Miranda Z, Fernandez Caroline S, Chung Amy, Dale C Jane, De Rose Robert, Lin Jie, Brooks Andrew G, Krebs Kendall C, Watkins David I, O'Connor David H, Davenport Miles P, Kent Stephen J
Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic., Australia.
J Med Primatol. 2005 Oct;34(5-6):282-93. doi: 10.1111/j.1600-0684.2005.00126.x.
The pigtail macaque (Macaca nemestrina) is a common model for the study of AIDS. The pigtail major histocompatibility complex class I allele Mane-A10 restricts an immunodominant simian immunodeficiency virus (SIV) Gag epitope (KP9) which rapidly mutates to escape T cell recognition following acute simian/human immunodeficiency virus infection. Two technologies for the detection of Mane-A10 in outbred pigtail macaques were developed: reference strand-mediated conformational analysis and sequence-specific primer polymerase chain reaction. A Mane-A10/KP9 tetramer was then developed to quantify CD8(+) T lymphocytes primed by multigenic DNA vaccination, which have previously been difficult to detect using standard interferon-gamma-based T cell assays. We also demonstrate mutational escape at KP9 following acute SIV infection. Mane-A10(+) animals have lower set point SIV levels than Mane-A*10(-) animals, suggesting a significant fitness cost of escape. These studies pave the way for a more robust understanding of HIV vaccines in pigtail macaques.
豚尾猕猴(食蟹猴)是研究艾滋病的常用模型。豚尾主要组织相容性复合体I类等位基因Mane - A10限制了一个免疫显性猿猴免疫缺陷病毒(SIV)Gag表位(KP9),在急性猿猴/人类免疫缺陷病毒感染后,该表位会迅速突变以逃避T细胞识别。开发了两种用于检测远交豚尾猕猴中Mane - A10的技术:参考链介导的构象分析和序列特异性引物聚合酶链反应。随后开发了一种Mane - A10/KP9四聚体,用于定量由多基因DNA疫苗引发的CD8(+) T淋巴细胞,此前使用基于标准干扰素-γ的T细胞检测方法很难检测到这些细胞。我们还证明了急性SIV感染后KP9处的突变逃逸。Mane - A10(+)动物的SIV设定点水平低于Mane - A*10(-)动物,这表明逃逸存在显著的适应性代价。这些研究为更深入了解豚尾猕猴中的HIV疫苗铺平了道路。