Nicholas L. Truex, Somesh Mohapatra, Mariane Melo, Jacob Rodriguez, Na Li, Wuhbet Abraham, Deborah Sementa, Faycal Touti, Derin B. Keskin, Catherine J. Wu, Darrell J. Irvine, Rafael Gómez-Bombarelli* and Bradley L. Pentelute*,
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引用次数: 0
Abstract
Antigen processing is critical for therapeutic vaccines to generate epitopes for priming cytotoxic T cell responses against cancer and pathogens, but insufficient processing often limits the quantity of epitopes released. We address this challenge using machine learning to ascribe a proteasomal degradation score to epitope sequences. Epitopes with varying scores were translocated into cells using nontoxic anthrax proteins. Epitopes with a low score show pronounced immunogenicity due to antigen processing, but epitopes with a high score show limited immunogenicity. This work sheds light on the sequence–activity relationships between proteasomal degradation and epitope immunogenicity. We anticipate that future efforts to incorporate proteasomal degradation signals into vaccine designs will lead to enhanced cytotoxic T cell priming by these vaccines in clinical settings.
Design of cytotoxic T cell epitopes for enhancing antigen processing and presentation, enabled by machine learning of human degrons and cytosolic delivery with two anthrax proteins.
抗原处理对于治疗性疫苗产生表位以引发细胞毒性 T 细胞对癌症和病原体的反应至关重要,但处理不足往往会限制表位的释放量。我们利用机器学习对表位序列进行蛋白酶体降解评分,以应对这一挑战。使用无毒炭疽蛋白将不同分数的表位转运到细胞中。得分低的表位因抗原处理而显示出明显的免疫原性,但得分高的表位则显示出有限的免疫原性。这项研究揭示了蛋白酶体降解与表位免疫原性之间的序列活性关系。我们预计,未来将蛋白酶体降解信号纳入疫苗设计的努力将使这些疫苗在临床环境中增强细胞毒性 T 细胞的引诱作用。
期刊介绍:
ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.