Scheiblhofer Sandra, Laimer Josef, Machado Yoan, Weiss Richard, Thalhamer Josef
a Department of Molecular Biology , University of Salzburg , Salzburg , Austria.
Expert Rev Vaccines. 2017 May;16(5):479-489. doi: 10.1080/14760584.2017.1306441. Epub 2017 Mar 24.
In modern vaccinology and immunotherapy, recombinant proteins more and more replace whole organisms to induce protective or curative immune responses. Structural stability of proteins is of crucial importance for efficient presentation of antigenic peptides on MHC, which plays a decisive role for triggering strong immune reactions. Areas covered: In this review, we discuss structural stability as a key factor for modulating the potency of recombinant vaccines and its importance for antigen proteolysis, presentation, and stimulation of B and T cells. Moreover, the impact of fold stability on downstream events determining the differentiation of T cells into effector cells is reviewed. We summarize studies investigating the impact of protein fold stability on the outcome of the immune response and provide an overview on computational methods to estimate the effects of point mutations on protein stability. Expert commentary: Based on this information, the rational design of up-to-date vaccines is discussed. A model for predicting immunogenicity of proteins based on their conformational stability at different pH values is proposed.
在现代疫苗学和免疫疗法中，重组蛋白越来越多地取代全生物体来诱导保护性或治愈性免疫反应。蛋白质的结构稳定性对于抗原肽在主要组织相容性复合体（MHC）上的有效呈递至关重要，而MHC在触发强烈免疫反应中起决定性作用。涵盖领域：在本综述中，我们讨论结构稳定性作为调节重组疫苗效力的关键因素及其对抗原蛋白水解、呈递以及B细胞和T细胞刺激的重要性。此外，还综述了折叠稳定性对决定T细胞分化为效应细胞的下游事件的影响。我们总结了研究蛋白质折叠稳定性对免疫反应结果影响的研究，并概述了用于估计点突变对蛋白质稳定性影响的计算方法。专家评论：基于这些信息，讨论了新型疫苗的合理设计。提出了一种基于蛋白质在不同pH值下的构象稳定性预测其免疫原性的模型。
