PRIMARY ANTIBODY-RESPONSES TO A WELL-DEFINED AND UNIQUE HAPTEN ARE NOT ENHANCED BY PREIMMUNIZATION WITH CARRIER - ANALYSIS IN A VIRAL MODEL
PRIMARY ANTIBODY-RESPONSES TO A WELL-DEFINED AND UNIQUE HAPTEN ARE NOT ENHANCED BY PREIMMUNIZATION WITH CARRIER - ANALYSIS IN A VIRAL MODEL
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DOI：
10.1073/pnas.83.8.2604
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发表时间：
1986-04-01
影响因子：
11.1
通讯作者：
ZINKERNAGEL, RM
中科院分区：
文献类型：
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作者：
GUPTA, SC;HENGARTNER, H;ZINKERNAGEL, RM
我们使用病毒模型重新检查经典实验，表明先前单独用“载体”分子引发，然后用载体-半抗原缀合物激发的小鼠表现出增强的抗半抗原抗体应答。用活的或UV灭活的水泡性口炎病毒（VSV）印第安纳州（Ind）血清型（含或不含完全弗氏佐剂）致敏小鼠。用VSV新泽西（NJ）攻击后，这些小鼠产生了抗VSV-Ind和VSV-NJ的第二型IgG应答，通过ELISA中的抗体结合测定。在用VSV-NJ致敏小鼠的交互实验中发现了相同的结果。类似地，当小鼠用Ind或NJ血清型的活VSV、UV灭活VSV或纯化VSV糖蛋白G致敏，随后用二硝基苯基（N2 ph）缀合的UV灭活VSV或任一血清型的N2 ph缀合的G蛋白攻击时，它们表现出第二型抗N2 ph抗体应答，如通过ELISA测量的IgG与二硝基苯基化牛血清白蛋白的结合所证明的。相比之下，当监测中和抗体应答时，用VSV-NJ攻击的VSV-Ind致敏小鼠产生了严格的初级类型的抗VSV-NJ应答，反之亦然。我们的结论是，预先存在的辅助T细胞特异性的共享载体决定因素不改善处女B细胞的反应，具体的“新的”，独特的决定因素，是生物相关的中和抗体的目标。这些发现表明，引发的B细胞，而不是辅助T细胞可能是重要的，以诱导抗体介导的保护性免疫。
We used a viral model to reexamine classical experiments showing that mice previously primed with a "carrier" molecule alone and then challenged with the carrier-hapten conjugate exhibited an enhanced antihapten antibody response. Mice were primed with live or UV-inactivated vesicular stomatitis virus (VSV) Indiana (Ind) serotype with or without complete Freund''s adjuvant. After challenge with VSV New Jersey (NJ), these mice developed a secondary-type IgG response, measured by antibody binding in an ELISA, against both VSV-Ind and VSV-NJ. The same result was found for the reciprocal experiments where mice were primed with VSV-NJ. Similarly, when mice were primed with live VSV, UV-inactivated VSV, or purified VSV glycoprotein G of Ind or NJ serotype and later were challenged with dinitrophenyl (N2ph)-conjugated, UV-inactivated VSV or with N2ph-conjugted G protein of either serotype, they exhibited a secondary-type anti-N2ph antibody response as demonstrated by the binding of IgG to dinitrophenylated bovine serum albumin measured by ELISA. In contrast, when neutralizing antibody responses were monitored, VSV-Ind-primed mice challenged with VSV-NJ developed a strictly primary type of anti-VSV-NJ response and vice versa. We conclude that preexistent helper T cells specific for shared carrier determinants do not improve virgin B-cell responses specific for "new", unique determinants that are the target for the biologically relevant neutralizing antibodies. These findings suggest that priming of B cells rather than of helper T cells may be of importance to induce protective immunity mediated by antibodies.