Department of Biochemistry & Molecular Biology, University of Bari, Bari 70126, Italy.
Immunotherapy. 2011 Jan;3(1):49-58. doi: 10.2217/imt.10.83.
Cross-reactivity may affect diagnostic tests and cause harmful autoimmune reactions following immunotherapy. To predict potential cross-reactivity and search for safe immunotherapeutic approaches, we analyzed sequence identity between microbial antigens and the human proteome. Using diphtheria toxin (DT) as a model, we examined its patterns of identity with human proteins at the pentapeptide level. DT shares 503 pentapeptides with the human proteome, while only 31 pentapeptides are unique to the toxin. DT pentapeptide identity involves multiple/repeated matches in human proteins (a total of 4966 occurrences). Human proteins containing bacterial peptide matches include antigens linked to fundamental cellular functions, such as cell cycle control, proliferation, development and differentiation. The data presented in this article offer a rational basis for designing peptide-based vaccines that specifically target DT and thus eliminate the potential risk of cross-reactivity with human proteins. More generally, this study proposes a methodological approach for avoiding cross-reactivity in immune reactions.
交叉反应性可能会影响诊断性检测，并在免疫治疗后引起有害的自身免疫反应。为了预测潜在的交叉反应性并寻找安全的免疫治疗方法，我们分析了微生物抗原与人类蛋白质组之间的序列同一性。我们使用白喉毒素（DT）作为模型，研究了其在五肽水平上与人蛋白的同一性模式。DT 与人蛋白质组共享 503 个五肽，而毒素特有的五肽只有 31 个。DT 五肽同一性涉及人类蛋白质中的多次/重复匹配（总共有 4966 次出现）。含有细菌肽匹配的人类蛋白包括与基本细胞功能相关的抗原，如细胞周期控制、增殖、发育和分化。本文提供的数据为设计针对 DT 的基于肽的疫苗提供了合理的基础，从而消除了与人类蛋白发生交叉反应的潜在风险。更一般地说，这项研究提出了一种在免疫反应中避免交叉反应性的方法学方法。
