抗原提呈动力学对T细胞扩增的调控
Regulation of T cell expansion by antigen presentation dynamics
摘要：
适应性免疫系统的一个基本特征是在免疫反应期间抗原特异性淋巴细胞的增殖以形成效应细胞的大池。必须调节这种增殖以确保对感染的有效反应，同时避免免疫病理学。最近在小鼠中的实验已经证明，响应于同源抗原的T细胞的特定克隆的扩增相对于T细胞的初始数量服从显著的逆幂定律。在这里，我们表明，这种关系自然产生的模型中，T细胞的扩增是有限的衰减水平的抗原。相同的模型还解释了观察到的T细胞扩增对抗原亲和力和抗原施用动力学的依赖性。扩展该模型以解决竞争抗原的多个T细胞克隆的扩增，我们发现较高亲和力的克隆可以抑制较低亲和力克隆的增殖，从而促进反应的特异性。采用该模型来获得最佳的疫苗接种方案，我们发现，指数增加的抗原剂量可以实现接近优化的反应。因此，我们得出结论，抗原的动态是一个关键的调节器的大小和特异性的适应性免疫反应。
英文摘要：
An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology. Recent experiments in mice have demonstrated that the expansion of a specific clone of T cells in response to cognate antigen obeys a striking inverse power law with respect to the initial number of T cells. Here, we show that such a relationship arises naturally from a model in which T cell expansion is limited by decaying levels of presented antigen. The same model also accounts for the observed dependence of T cell expansion on affinity for antigen and on the kinetics of antigen administration. Extending the model to address expansion of multiple T cell clones competing for antigen, we find that higher affinity clones can suppress the proliferation of lower affinity clones, thereby promoting the specificity of the response. Employing the model to derive optimal vaccination protocols, we find that exponentially increasing antigen doses can achieve a nearly optimized response. We thus conclude that the dynamics of presented antigen is a key regulator of both the size and specificity of the adaptive immune response.
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