Infofusion, Systems Biology Research Centre, School of Life Sciences, University of Skövde, Skövde, Sweden.
Biophys J. 2010 Nov 3;99(9):2717-25. doi: 10.1016/j.bpj.2010.08.024.
T cells continuously search for antigenic peptides presented on major histocompatibility complexes expressed on nearly all nucleated cells. Because only a few antigenic peptides are presented in a sea of thousands of self-peptides, the T cells have a critical task in discriminating between self- and nonself-peptides. This search process for antigens must be performed with sufficient speed in order to induce a fast response against invading pathogens. This study presents a mathematical framework for analyzing the scanning process of peptides. The framework includes analytic expressions for calculating the sampling rate as well as continuous-systems- and stochastic-agent-based models. The results show that the scanning of self-peptides is a very fast process due to fast off-rates. The simulations also predict the existence of an optimal sampling rate for a certain range of on-rates based on the recently proposed confinement time model. Calculations reveal that most of the self-peptides located within a microdomain are scanned within just a few seconds, and that the T cell receptors have kinetics for self-peptides, facilitating fast scanning. The derived mathematical expressions within this study provide conceptual calculations for further investigations of how the T cell discriminates between self- and nonself-peptides.
T 细胞持续搜索主要组织相容性复合体上呈现的抗原肽，这些抗原肽几乎存在于所有有核细胞上。由于只有少数抗原肽在成千上万的自身肽中呈现，因此 T 细胞在区分自身肽和非自身肽方面具有重要任务。为了对入侵病原体产生快速反应，这种抗原搜索过程必须以足够的速度进行。本研究提出了一个用于分析肽扫描过程的数学框架。该框架包括用于计算采样率的解析表达式以及连续系统和基于随机主体的模型。结果表明，由于快速的脱离率，自身肽的扫描是一个非常快速的过程。模拟还根据最近提出的限制时间模型预测了在一定的进入率范围内存在最佳采样率的情况。计算结果表明，位于微域内的大多数自身肽在短短几秒钟内就被扫描到了，而且 T 细胞受体对自身肽具有动力学特性，这有助于快速扫描。本研究中推导的数学表达式为进一步研究 T 细胞如何区分自身肽和非自身肽提供了概念性计算。
