Institute of Physics, Polish Academy of Sciences, Al. Lotników 32/46, 02-668 Warsaw, Poland.
Department of Theory and Bio-Systems, Max Planck Institut of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
Cells. 2021 Apr 26;10(5):1023. doi: 10.3390/cells10051023.
T cells are sensitive to 1 to 10 foreign-peptide-MHC complexes among a vast majority of self-peptide-MHC complexes, and discriminate selectively between peptide-MHC complexes that differ not much in their binding affinity to T-cell receptors (TCRs). Quantitative models that aim to explain this sensitivity and selectivity largely focus on single TCR/peptide-MHC complexes, but T cell adhesion involves a multitude of different complexes. In this article, we demonstrate in a three-dimensional computational model of T-cell adhesion that the cooperative stabilization of close-contact zones is sensitive to one to three foreign-peptide-MHC complexes and occurs at a rather sharp threshold affinity of these complexes, which implies selectivity. In these close-contact zones with lateral extensions of hundred to several hundred nanometers, few TCR/foreign-peptide-MHC complexes and many TCR/self-peptide-MHC complexes are segregated from LFA-1/ICAM-1 complexes that form at larger membrane separations. Previous high-resolution microscopy experiments indicate that the sensitivity and selectivity in the formation of closed-contact zones reported here are relevant for T-cell recognition, because the stabilization of close-contact zones by foreign, agonist peptide-MHC complexes precedes T-cell signaling and activation in the experiments.
T 细胞对大量自身肽-MHC 复合物中的 1 至 10 个外来肽-MHC 复合物敏感，并在 TCR 结合亲和力差异不大的肽-MHC 复合物之间选择性区分。旨在解释这种敏感性和选择性的定量模型主要集中在单个 TCR/肽-MHC 复合物上，但 T 细胞黏附涉及多种不同的复合物。在本文中，我们在 T 细胞黏附的三维计算模型中证明，紧密接触区的协同稳定对 1 至 3 个外来肽-MHC 复合物敏感，并且发生在这些复合物相当尖锐的亲和力阈值，这意味着具有选择性。在这些具有数百到数百纳米侧向延伸的紧密接触区中，很少有 TCR/外来肽-MHC 复合物和许多 TCR/自身肽-MHC 复合物与在较大膜分离下形成的 LFA-1/ICAM-1 复合物隔离。先前的高分辨率显微镜实验表明，这里报道的封闭接触区形成中的敏感性和选择性与 T 细胞识别相关，因为外来激动肽-MHC 复合物稳定紧密接触区先于实验中的 T 细胞信号转导和激活。
