Dynamical footprint of cross-reactivity in a human autoimmune T-cell receptor.
Dynamical footprint of cross-reactivity in a human autoimmune T-cell receptor.
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DOI：
10.1038/srep42496
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发表时间：
2017-02-14
影响因子：
4.6
通讯作者：
Delogu F
中科院分区：
文献类型：
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作者：
Kumar A;Delogu F
本工作的重点是髓鞘蛋白（MBP）自身肽和两种微生物肽（UL 15，PMM）之间的Hy.1B11 T细胞受体（TCR）的交叉反应性的动力学方面。从患有多发性硬化症（MS）的患者中分离出相同的TCR。该研究旨在突出TCR与主要组织相容性复合物（MHC）蛋白质呈递的肽之间的识别机制的化学相互作用，这些蛋白质构成了针对外源抗原的适应性免疫反应的关键组成部分。由于TCR识别由MHC呈递的不同肽抗原的能力取决于其交叉反应性，我们使用分子动力学方法获得TCR-肽-MHC复合物的原子细节。我们的研究结果表明，Hy.1B11 TCR的交叉反应性的动力学基础是如何植根于一个类似的跨TCR-肽-MHC界面的桥接相互作用模式。我们的模拟证实了TCR CDR 3 α E98残基与MHC相互作用的重要性以及P6肽残基在MHC结合亲和力中的主导作用。总而言之，我们的研究提供了充满活力和动态的洞察因素，管理肽识别的交叉反应Hy.1B11 TCR，发现在MS患者。
The present work focuses on the dynamical aspects of cross-reactivity between myelin based protein (MBP) self-peptide and two microbial peptides (UL15, PMM) for Hy.1B11 T-cell receptor (TCR). This same TCR was isolated from a patient suffering from multiple sclerosis (MS). The study aims at highlighting the chemical interactions underlying recognition mechanisms between TCR and the peptides presented by Major Histocompatibility Complex (MHC) proteins, which form a crucial component in adaptive immune response against foreign antigens. Since the ability of a TCR to recognize different peptide antigens presented by MHC depends on its cross-reactivity, we used molecular dynamics methods to obtain atomistic detail on TCR-peptide-MHC complexes. Our results show how the dynamical basis of Hy.1B11 TCR’s cross-reactivity is rooted in a similar bridging interaction pattern across the TCR-peptide-MHC interface. Our simulations confirm the importance of TCR CDR3α E98 residue interaction with MHC and a predominant role of P6 peptide residue in MHC binding affinity. Altogether, our study provides energetic and dynamical insights into factors governing peptide recognition by the cross-reactive Hy.1B11 TCR, found in MS patient.