Laws of mechanics and function in proteins as evolved molecular machines

项目总结/摘要 适应性免疫系统已经进化到能够记住特定抗原的初次暴露， 对后续曝光的有效攻击。然而，快速进化的病毒，如流感和艾滋病毒， 当它们变异时，对人类免疫系统的新挑战，使它们更难识别和应对 在随后的曝光中。为了使对这些病原体的次级反应成功， 反应必须产生记忆反应，平衡对原始抗原的特异性和多样性 与后续暴露的多种可能变体进行对比。对于某一物种的个体来说 与更大群体中的其他个体相互作用，特异性之间给定平衡的功效 多样性取决于许多因素，包括个人暴露于相同环境的可能性 病原体在未来，抗原突变的速度，以及对生物过程的限制 它们控制着该物种内免疫记忆的产生。该研究计划旨在 构建一个理论框架，描述与多样性相关的利益和权衡， 适应性免疫应答和产生所述多样性的机制。本研究将使用 对几个数据集进行计算分析，以评估不同抗体应答的程度。 利用小鼠和人类， 作为代表性的例子。

PROJECT SUMMARY/ABSTRACT The adaptive immune system has evolved to remember primary exposures to specific antigens and launch effective attacks to subsequent exposures. However, rapidly evolving viruses like influenza and HIV present new challenges to the human immune system as they mutate, making them harder to recognize and respond to during subsequent exposures. In order for secondary responses to these pathogens to succeed, the primary response must generate a memory response that balances specificity to the original antigen with diversity against the multitude of possible variants of subsequent exposures. For an individual of a given species interacting with other individuals within a larger population, the efficacy of a given balance between specificity and diversity depends on a number of factors, including how likely the individual is to be exposed to the same pathogen in the future, the rate at which the antigen is mutating, and constraints on the biological processes which control the generation of immunological memory within that species. This research program aims to construct a theoretical framework for characterizing the benefits and trade-offs associated with diversity in the adaptive immune response and the mechanisms by which said diversity is generated. This study will then use computational analyses of several datasets to evaluate the extent to which the antibody responses of different species generate levels of diversity which are well-adapted to their biological needs, using mice and humans as representative examples.