Microtubule elasticity: connecting all-atom simulations with continuum mechanics.
Microtubule elasticity: connecting all-atom simulations with continuum mechanics.
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DOI：
10.1016/j.bpj.2008.12.596
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发表时间：
2009-02
影响因子：
8.6
通讯作者：
D. Sept;F. MacKintosh
中科院分区：
文献类型：
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作者：
D. Sept;F. MacKintosh
肯尼·K·陈，洪深。华盛顿大学，西雅图，美国华盛顿州。树突状细胞(DC)对T淋巴细胞(CD4或CD8)的刺激是启动和建立针对病原体的免疫应答的关键事件。了解支配DC如何获取、处理和呈递抗原的细胞内机制将导致更合理的疫苗设计。虽然单个细胞内事件已经被阐明，但缺乏关于不同的抗原运输网络如何影响T细胞刺激的定量观点。在这项工作中，我们开发了一个随机模型来研究T细胞刺激的抗原递送的关键步骤，包括抗原内化、在内小体/溶酶体环境中的运输、获得各种抗原递呈途径以及刺激CD4或CD8塔T细胞。各种过程的动力学参数要么是从以前的报告中获得的，要么是从我们自己的实验数据中得出的。特别是，我们的目标是确定调节T细胞刺激的抗原运输和处理的限速步骤。此外，我们还研究了疫苗的特性，如靶向配体的大小和附着，如何影响所递送的抗原是否刺激CD4和CD8的T细胞反应。抗原递送计算模型的发展将导致更深入地了解T细胞反应类型所涉及的细胞内过程，并更合理地设计有效的疫苗。
Kenny K. Tran, Hong Shen. University of Washington, Seattle, WA, USA. The stimulation of T lymphocytes (CD4þ or CD8þ) by dendritic cells (DCs) is a key event in the initiation and establishment of immune responses against pathogens. Understanding the intracellular mechanisms that govern how DCs acquire, process, and present antigens would lead to more rational vaccine design. Although individual intracellular events have been elucidated, a quantitative view of how the various networks of antigen trafficking affect T cell stimulation is lacking. In this work, we developed a stochastic model to examine the critical steps involved in antigen delivery for T cell stimulation, including antigen internalization, trafficking in endosomal/lysosomal environments, access to various antigen presentation pathways, and stimulation of either CD4þ or CD8þ T cells. Kinetic parameters for various processes were either obtained from previous reports if available, or derived from our own experimental data. In particular, we aim to identify rate-limiting steps of antigen trafficking and processing that regulate T cell stimulation. Furthermore, we examine how characteristics of the vaccine, such as size and attachment of targeting ligands, affect whether delivered antigen stimulates CD4þ or CD8þ T cell responses. The development of the computation model of antigen delivery will lead to greater insight into the intracellular processes involved in the type of T cell response elicited and to more rational design of effective vaccines.