Yu M W, Lemieux S, Talbot P J
Laboratory of Neuroimmunovirology, Institut Armand-Frappier, Université du Québec, Laval, Canada.
Eur J Immunol. 1996 Dec;26(12):3230-3. doi: 10.1002/eji.1830261258.
The idiotypic network can be experimentally altered to induce protective immune responses against microbial pathogens. Both internal image and noninternal image anti-idiotypic (anti-Id) antibodies have been shown to trigger antigen (Ag)-specific immune responses. Therefore, mechanisms of anti-Id vaccination appear to go beyond structural mimicry of Ag, but remain undefined. Using the neurotropic murine coronavirus animal model, we have previously shown that a polyclonal noninternal image anti-Id (Ab2) could vaccinate BALB/c mice. To characterize its mode of action, we have examined the immune modulating capability of this Ab2 in vivo in strains of mice with different H-2 haplotypes. Even though only internal image anti-Id are expected to induce non-genetically restricted immunity, this noninternal image Ab2 induced protective immunity in four of eight genetically different strains of mice susceptible to coronavirus infection. These were BALB/c (H-2d), DBA/2 (H-2d), DBA/1 (H-2q), and SWR (H-2q) mice. Protection was generally correlated with the induction of specific antiviral Ab (Ab3) that showed biological properties, such as virus neutralization in vitro, similar to the initial Ab1. To evaluate the genetic implication of the H-2 haplotypes in protection, congenic mice were also tested. Vaccination profiles suggest that cooperation between background gene(s) of the BALB/c mouse with H-2d and H-2q loci is necessary for an optimal protective immune response, although the main genetic element(s) regulating the antiviral response to Ab2 inoculation appeared to be located outside the major histocompatibility complex. These results are consistent with the ability of Ab2 to induce protective antiviral antibodies in genetically different animals by biological mimicry.
独特型网络可通过实验进行改变，以诱导针对微生物病原体的保护性免疫反应。已证明内影像和非内影像抗独特型（抗Id）抗体均可触发抗原（Ag）特异性免疫反应。因此，抗Id疫苗接种的机制似乎超出了Ag的结构模拟，但仍未明确。利用嗜神经性小鼠冠状病毒动物模型，我们先前已表明多克隆非内影像抗Id（Ab2）可使BALB/c小鼠接种疫苗。为了表征其作用模式，我们在具有不同H-2单倍型的小鼠品系中体内检测了这种Ab2的免疫调节能力。尽管预计只有内影像抗Id可诱导非基因限制的免疫，但这种非内影像Ab2在八种对冠状病毒感染敏感的基因不同的小鼠品系中的四种中诱导了保护性免疫。这些小鼠是BALB/c（H-2d）、DBA/2（H-2d）、DBA/1（H-2q）和SWR（H-2q）小鼠。保护作用通常与特异性抗病毒抗体（Ab3）的诱导相关，该抗体表现出与初始Ab1相似的生物学特性，如体外病毒中和。为了评估H-2单倍型在保护中的遗传影响，还测试了同源基因小鼠。疫苗接种情况表明，尽管调节对Ab2接种的抗病毒反应的主要遗传元件似乎位于主要组织相容性复合体之外，但BALB/c小鼠具有H-2d和H-2q位点的背景基因之间的合作对于最佳保护性免疫反应是必要的。这些结果与Ab2通过生物学模拟在基因不同的动物中诱导保护性抗病毒抗体的能力一致。
