State Key Laboratory of Nonlinear Mechanics (LNM) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China.
International Center for Applied Mechanics, State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace, Xi'an Jiaotong University, Xi'an, 710049, China.
Phys Rev E. 2017 Jan;95(1-1):012403. doi: 10.1103/PhysRevE.95.012403. Epub 2017 Jan 10.
The interactions between T-cell receptor (TCR) and peptide-major-histocompatibility complex (pMHC), which enable T-cell development and initiate adaptive immune responses, have been intensively studied. However, a central issue of how lipid rafts affect the TCR-pMHC interactions remains unclear. Here, by using a statistical-mechanical membrane model, we show that the binding affinity of TCR and pMHC anchored on two apposing cell membranes is significantly enhanced because of the lipid raft-induced signaling protein aggregation. This finding may provide an alternative insight into the mechanism of T-cell activation triggered by very low densities of pMHC. In the case of cell-substrate adhesion, our results indicate that the loss of lateral mobility of the proteins on the solid substrate leads to the inhibitory effect of lipid rafts on TCR-pMHC interactions. Our findings help to understand why different experimental methods for measuring the impact of lipid rafts on the receptor-ligand interactions have led to contradictory conclusions.
T 细胞受体 (TCR) 与肽-主要组织相容性复合物 (pMHC) 之间的相互作用，使 T 细胞得以发育并启动适应性免疫反应，这一过程已得到深入研究。然而，脂质筏如何影响 TCR-pMHC 相互作用这一核心问题仍不清楚。在这里，我们通过使用统计力学膜模型，表明由于脂质筏诱导的信号蛋白聚集，锚定在两个相邻细胞膜上的 TCR 和 pMHC 的结合亲和力显著增强。这一发现可能为 pMHC 极低密度触发 T 细胞激活的机制提供了另一种见解。在细胞-底物黏附的情况下，我们的结果表明，固体底物上蛋白质的横向流动性丧失导致脂质筏对 TCR-pMHC 相互作用的抑制效应。我们的研究结果有助于理解为什么不同的实验方法测量脂质筏对受体-配体相互作用的影响会导致相互矛盾的结论。
