School of Mathematics and Statistics, College of Science and Engineering, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Proc Biol Sci. 2013 Jan 2;280(1753):20122129. doi: 10.1098/rspb.2012.2129. Print 2013 Feb 22.
Systems that generate antigenic variation enable pathogens to evade host immune responses and are intricately interwoven with major pathogen traits, such as host choice, growth, virulence and transmission. Although much is understood about antigen switching at the molecular level, little is known about the cross-scale links between these molecular processes and the larger-scale within and between host population dynamics that they must ultimately drive. Inspired by the antigenic variation system of African trypanosomes, we apply modelling approaches to our expanding understanding of the organization and expression of antigen repertoires, and explore links across these scales. We predict how pathogen population processes are determined by underlying molecular genetics and infer resulting selective pressures on important emergent repertoire traits.
能够产生抗原变异的系统使病原体能够逃避宿主的免疫反应，并且与主要病原体特征（如宿主选择、生长、毒力和传播）错综复杂地交织在一起。尽管在分子水平上对抗原转换有了很多了解，但对于这些分子过程与它们最终必须驱动的更大规模的宿主种群动态之间的跨尺度联系却知之甚少。受非洲锥虫抗原变异系统的启发，我们将建模方法应用于我们对抗原库的组织和表达的不断扩大的理解，并探索这些尺度之间的联系。我们预测病原体种群过程是如何由潜在的分子遗传学决定的，并推断对重要涌现的库特征的选择压力。
