Schöll I, Wiedermann U, Förster-Waldl E, Ganglberger E, Baier K, Boltz-Nitulescu G, Scheiner O, Ebner C, Jensen-Jarolim E
Department of Pathophysiology, University of Vienna, Austria.
Clin Exp Allergy. 2002 Nov;32(11):1583-8. doi: 10.1046/j.1365-2222.2002.01527.x.
In previous studies we have generated mimotopes of Bet v 1, the major birch pollen allergen, by biopannings of phage-display random peptide libraries. In the present study, we analysed the humoral and cellular immune response to Bet v 1-mimotopes.
The mimotope CFPYCYPSESA, designated Bet mim 1, was used for intraperitoneal immunizations of BALB/c mice in phage-displayed form. For examination of the humoral immune response, enzyme-linked immunosorbent assay (ELISA) experiments were applied. Stimulation capacities were investigated in cultured mouse splenocytes and in humoral Bet v 1-specific T cell clones.
We demonstrated that the Bet mim 1-induced murine antibody response against Bet v 1 was predominated by the IgG1 isotype. In these mice only the phage-displayed mimotopes, but neither the allergen nor the synthetic Bet mim 1-mimotopes were able to stimulate proliferation of cultured splenocytes. Using Bet v 1-specific T cell clones of allergic patients, phage-displayed and synthetic mimotopes were unable to stimulate T cell proliferation. Moreover, tolerance induction to Bet v 1 in mice by intranasal administration of Bet mim 1-phages or Bet mim 1-peptide failed.
Taking these results together, our data indicate that Bet mim 1 mimics a Bet v 1-epitope on the B cell but not on the T cell level. We suggest that the phage itself is responsible for the recruitment of T cells providing bystander help in the formation of a mimotope-specific humoral response.
在先前的研究中，我们通过噬菌体展示随机肽库的生物淘选技术，获得了主要桦树花粉过敏原Bet v 1的模拟表位。在本研究中，我们分析了针对Bet v 1模拟表位的体液免疫和细胞免疫反应。
将指定为Bet mim 1的模拟表位CFPYCYPSESA以噬菌体展示形式用于BALB/c小鼠的腹腔免疫。为检测体液免疫反应，应用了酶联免疫吸附测定（ELISA）实验。在培养的小鼠脾细胞和体液中Bet v 1特异性T细胞克隆中研究刺激能力。
我们证明，Bet mim 1诱导的针对Bet v 1的小鼠抗体反应以IgG1同种型为主。在这些小鼠中，只有噬菌体展示的模拟表位，而过敏原和合成的Bet mim 1模拟表位均不能刺激培养的脾细胞增殖。使用过敏患者的Bet v 1特异性T细胞克隆，噬菌体展示的和合成的模拟表位均不能刺激T细胞增殖。此外，通过鼻内给予Bet mim 1噬菌体或Bet mim 1肽未能诱导小鼠对Bet v 1的耐受。
综合这些结果，我们的数据表明Bet mim 1在B细胞水平而非T细胞水平模拟了Bet v 1表位。我们认为噬菌体本身负责募集T细胞，在模拟表位特异性体液反应形成过程中提供旁观者辅助。
