Chackerian B, Lowy D R, Schiller J T
Laboratory of Cellular Oncology, National Institutes of Health, Building 36, Room 1D-32, Bethesda, MD 20892-4040, USA.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2373-8. doi: 10.1073/pnas.96.5.2373.
The vertebrate immune system has evolved to respond vigorously to microbial infection but to ignore self-antigens. Evidence has emerged that B cell responses to viruses are initiated by immune recognition of ordered arrays of antigen on the viral surface. To test whether autoantibodies against a self-antigen can be induced by placing it in a context that mimics the ordered surface of a viral particle, a peptide representing an extracellular loop of the mouse chemokine receptor CCR5 was incorporated into an immunodominant site of the bovine papillomavirus virus L1 coat protein, which self-assembles into virus-like particles. Mice inoculated with chimeric L1-CCR5 particles generated autoantibodies that bound to native mouse CCR5, inhibited binding of its ligand RANTES, and blocked HIV-1 infection of an indicator cell line expressing a human-mouse CCR5 chimera. These results suggest a general method for inducing autoantibodies against self-antigens, with diverse potential basic research and clinical applications.
脊椎动物的免疫系统已经进化到能够对微生物感染做出强烈反应，同时忽略自身抗原。有证据表明，B细胞对病毒的反应是由对病毒表面有序排列的抗原的免疫识别引发的。为了测试针对自身抗原的自身抗体是否能通过将其置于模拟病毒颗粒有序表面的环境中而被诱导产生，一种代表小鼠趋化因子受体CCR5细胞外环的肽被整合到牛乳头瘤病毒L1衣壳蛋白的免疫显性位点，该蛋白可自组装成病毒样颗粒。接种嵌合L1-CCR5颗粒的小鼠产生了与天然小鼠CCR5结合的自身抗体，抑制了其配体RANTES的结合，并阻断了表达人-小鼠CCR5嵌合体的指示细胞系的HIV-1感染。这些结果提示了一种诱导针对自身抗原的自身抗体的通用方法，具有多种潜在的基础研究和临床应用。
