Siokis Anastasios, Robert Philippe A, Meyer-Hermann Michael
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Rebenring 56, Braunschweig, 38106, Germany.
Institute de Génétique Moléculaire Montpellier, CNRS, Université Monpellier II, Montpellier, France.
Methods Mol Biol. 2017;1584:171-182. doi: 10.1007/978-1-4939-6881-7_12.
During antigen recognition by T cells, a specific spatial structure is formed at the contact face to an antigen-presenting cell (APC), called an immunological synapse (IS). The IS supports bidirectional signaling and release of effector molecules and is widely studied both biologically and numerically, in order to understand the process of T cell activation and signaling. This specialized structure harbors a central area (central supramolecular activation cluster, cSMAC) populated by T cell receptor-peptide-major histocompatibility complex (TCR-pMHC ) interactions, hedged by a peripheral ring (peripheral supramolecular activation cluster, pSMAC) of integrin lymphocyte function associated-1 interactions with its immunoglobulin superfamily ligand intercellular adhesion molecule-1 (LFA-1-ICAM-1). These two regions form the "bull's eye" pattern characteristic of the mature IS.In theoretical studies, different modeling architectures, including partial differential equations (PDE) and agent-based models , have been developed with the purpose to answer mechanistic questions about the IS dynamics. In this chapter, we explain possible physiological mechanisms that lead to the formation of ISs and technical issues that may occur in the course of development of agent-based models.
在T细胞识别抗原的过程中，与抗原呈递细胞（APC）的接触面会形成一种特定的空间结构，称为免疫突触（IS）。免疫突触支持双向信号传导和效应分子的释放，并且为了理解T细胞激活和信号传导过程，在生物学和数值方面都得到了广泛研究。这种特殊结构包含一个由T细胞受体 - 肽 - 主要组织相容性复合体（TCR - pMHC）相互作用构成的中心区域（中央超分子激活簇，cSMAC），其周围环绕着整合素淋巴细胞功能相关抗原1与其免疫球蛋白超家族配体细胞间黏附分子1（LFA - 1 - ICAM - 1）相互作用形成的外周环（外周超分子激活簇，pSMAC）。这两个区域形成了成熟免疫突触特有的“靶心”模式。在理论研究中，已经开发了不同的建模架构，包括偏微分方程（PDE）和基于主体的模型，目的是回答有关免疫突触动力学的机制问题。在本章中，我们解释了导致免疫突触形成的可能生理机制以及基于主体模型开发过程中可能出现的技术问题。
