Department of Biomedical Sciences and Human Oncology (DIMO), Rheumatologic and Systemic Autoimmune Diseases Unit, University of Bari Medical School, I-70124 Bari, Italy.
Int J Mol Sci. 2019 Apr 18;20(8):1920. doi: 10.3390/ijms20081920.
Antigen-mimicking peptide (mimotope)-based vaccines are one of the most promising forms of active-immunotherapy. The main drawback of this approach is that it induces antibodies that react poorly with the nominal antigen. The aim of this study was to investigate the molecular basis underlying the weak antibody response induced against the naïve protein after peptide vaccination. For this purpose, we analyzed the fine specificity of monoclonal antibodies (mAb) elicited with a 13-mer linear peptide, complementary to theantigen-combining site of the anti-CD20 mAb, Rituximab, in BALB/c mice. Anti-peptide mAb competed with Rituximab for peptide binding. Even so, they recognized a different antigenic motif from the one recognized by Rituximab. This explains their lack of reactivity with membrane (naïve) CD20. These data indicate that even on a short peptide the immunogenic and antigenic motifs may be different. These findings highlight an additional mechanism for epitope spreading and should be taken into account when designing peptides for vaccine purposes.
抗原模拟肽（ mimicope ）疫苗是最有前途的主动免疫疗法之一。这种方法的主要缺点是它诱导的抗体与名义抗原的反应性很差。本研究旨在探讨肽疫苗接种后诱导针对原始蛋白的弱抗体反应的分子基础。为此，我们分析了与抗 CD20 mAb 利妥昔单抗的抗原结合位点互补的 13 个线性肽诱导的单克隆抗体（ mAb ）的精细特异性在 BALB/c 小鼠中。抗肽 mAb 与利妥昔单抗竞争肽结合。即便如此，它们识别的抗原表位与利妥昔单抗识别的不同。这解释了它们与膜（原始）CD20 无反应性。这些数据表明，即使在短肽上，免疫原性和抗原性表位也可能不同。这些发现强调了表位扩展的另一种机制，在设计用于疫苗目的的肽时应考虑到这一点。
