打破耐受性:自身抗体可以靶向蛋白质翻译后修饰,Current Opinion in Biotechnology |
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自身抗体 (AAb) 是一种成熟的免疫学资源,可用于癌症检测和治疗。这种翻译的关键是更好地理解 AAb 在肿瘤组织中靶向但在正常组织中不结合的自身表位。已知自身蛋白的翻译后修饰 (PTM) 会破坏许多自身免疫性疾病的耐受性,并且最近在癌症中也有报道。可能的自身抗原的范围相当广泛,需要新的高维和高通量技术来探测这一库,以充分发挥其潜力。在这里,我们讨论了现有高通量检测 AAb 平台的优点和缺点,回顾了当前表征免疫原性 PTM 的方法,描述了识别疾病相关抗原的主要挑战,并提出了可能能够解决这些问题的未来技术的特性。这些挑战。我们的结论是,利用免疫系统的进化力量来区分自身和非自身具有转化为基于抗体的临床应用的巨大潜力。
"点击查看英文标题和摘要" Breaking tolerance: autoantibodies can target protein posttranslational modifications
Autoantibodies (AAb) are an immunological resource ripe for exploitation in cancer detection and treatment. Key to this translation is a better understanding of the self-epitope that AAb target in tumor tissue, but do not bind to in normal tissue. Posttranslational modifications (PTMs) on self-proteins are known to break tolerance in many autoimmune diseases and have also recently been described in cancer. This scope of possible autoantigens is quite broad and new high-dimensional and -throughput technologies to probe this repertoire will be necessary to fully exploit their potential. Here, we discuss the strengths and weaknesses of existing high-throughput platforms to detect AAb, review the current methods for characterizing immunogenic PTMs, describe the main challenges to identifying disease-relevant antigens and suggest the properties of future technologies that may be able to address these challenges. We conclude that exploiting the evolutionary power of the immune system to distinguish between self and nonself has great potential to be translated into antibody-based clinical applications. |
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